amine protection

8/9/2019 Amine Protection

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Amine protection (carbamates)- [Fmoc] [Boc] [Cbz] [Troc]

Side Chain protections- [Boc] (see carb. protections)

tBu - (tert-butyl) ester

Standard Protection Procedure

To a solution of te !-protected amino acid" #$%P (&.' e)" and tBu* (+., e) in dry #C$ at

& under an inert atmospere" is added #C/ (+.+. e) and stirred for , . Te mi0ture is ten

stirred at room temperature until complete by T1C (usually +2 ) and concentrated in vacuo.

Te residue is redissol3ed in etyl acetate and e0tracted t4ice 4it 4ater" ten t4ice 4it

aueous saturated sodium bicarbonate. Te or5anic solution is dried (ma5nesium sulfate) andconcentrated in vacuo. Te residue is purified by flas cromato5rapy (Si,) if necessary.

6emo3al

Te compound is dissol3ed in formic acid and stirred at room temperature until te reaction is

complete by T1C (usually +, ours). Te solution is ten concentrated and coconcentrated

se3eral times 4it toluene. Te resultin5 residue can ten be purified by flas cromato5rapy(Si,) if necessary.

6eferences

7. Cem. Soc." Per8in Trans. +" 1996" 9:'-99;.7C" 1982" 47" +9; )"
http://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Fmochttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Bochttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Cbzhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Trochttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#BocSideChainhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/Carbsynpage.htmlhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Tophttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/Carbsynmain.htmlhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Bochttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Cbzhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Trochttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#BocSideChainhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/Carbsynpage.htmlhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Tophttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/Carbsynmain.htmlhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Fmoc


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ten filtered and concentrated. Te resultin5 residue can ten be purified by flas

cromato5rapy (Si,) if necessary.

6eferences$acromolecules" 1978" ';2-';9.

[Bac8 to Top] [Bac8 to Syntetic Procedures]

Allyl- (allyl) ester


Te compound is dissol3ed in dry #C$ and allyl alcool (+.+ e) is added. Te solution is

stirred under an inert atmospere at & and dicycloe0ylcarbodiimide (+ e) is added follo4ed by

2-N,N-dimetylaminopyridine (&.&' e). Te reaction is allo4ed to 4arm to room temperatureand is stirred until complete by T1C (usually +-, days). tyl acetate is added and te resultin5

precipitate is remo3ed by filtration. Te filtrate is concentrated in vacuoand purified by flas


6emo3al

Te amino acid and pyrrolidine (+., e) are dissol3ed in metylene cloride and cooled to -+'.

Tripenylpospine (&., e) and Tetra8is(tripenylpospine)palladium (&) (&.&' e) are added

and stirred under an inert atmospere for appro0. + . ?ater and acetonitrile are added and teresultin5 mi0ture is e0tracted t4ice 4it petroleum eter. Te acetonitrile layer is e3aporated

and purified by flas cromato5rapy (Si,) if necessary.

6eferences

Tetraedron" 1996" 52" +,:;9-+,:',.[Bac8 to Top] [Bac8 to Syntetic Procedures]

PfP- (pentafluoropenyl) ester


Te acid is dissol3ed in etyl acetate and pentafluoropenol (+., e) is added. Te solution iscooled to & and #CC (+., e) is added. Te reaction is allo4ed to 4arm to room temperature

and stir until complete by T1C (usually o3erni5t" if not complete more #CC may be added).
http://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Tophttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/Carbsynmain.htmlhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Tophttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/Carbsynmain.htmlhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Tophttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/Carbsynmain.htmlhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Tophttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/Carbsynmain.html


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Te solution is ten filtered trou5 celite" rinsed se3eral times 4it t%c" and concentrated invacuo. Te resultin5 residue can ten be purified by flas cromato5rapy (Si,) if necessary.

6eferences

7. Cem. Soc." Per8in Trans. +" 1996" 9:'-99;.

[Bac8 to Top] [Bac8 to Syntetic Procedures]

e- (metyl) ester


Te compound is dissol3ed in dry $e* and tionyl cloride (, e) is added drop 4ise at &

under an inert atmospere. Te result is ten reflu0ed until complete by T1C (usually >2 ours)

and concentrated in vacuo. Te residue can ten be purified by flas cromato5rapy (Si,) ifnecessary.

6emo3al

Te ester is dissol3ed in metanol and +! !a* is added (e0cess). Te solution is ten eatedto reflu0 and stirred until complete by T1C (usually @+ ). Alacial acetic acid is added until te

mi0ture is neutral and ten diluted 4it cloroform. Te or5anic solution is e0tracted once 4it

4ater" once 4it brine" dried (ma5nesium sulfate)" and concentrated in vacuo. Te residue ispurified by flas cromato5rapy (Si,) if necessary.

6eferences

ur. 7. r5. Cem. 1999" ++,-++;'.

7C" 199!" 60" ,;+:-,;+9.[Bac8 to Top] [Bac8 to Syntetic Procedures]

PB- (para-meto0ybenzyl) ester


Te acid is dissol3ed in dry #C$ and 2-meto0ybenzyl alcool (+.+ e) is added. Te solution

is stirred under an inert atmospere at & and dicycloe0ylcarbodiimide (+ e) is added follo4edby 2-N,N-dimetylaminopyridine (&.&' e). Te reaction is allo4ed to 4arm to room

temperature and is stirred until complete by T1C (usually +-, days). tyl acetate is added and

te resultin5 precipitate is remo3ed by filtration. Te filtrate is concentrated in vacuo andpurified by flas cromato5rapy (Si,) if necessary.
http://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Tophttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/Carbsynmain.htmlhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Tophttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/Carbsynmain.htmlhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Tophttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/Carbsynmain.htmlhttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/AminoAcids.html#Tophttp://www.faculty.virginia.edu/mcgarveylab/Carbsyn/Carbsynmain.html


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6emo3al

Te ester is dissol3ed in penol and TF% (+-, e) is added under an inert atmospere at 2'. Te

reaction is stirred until complete by T1C (usually @, ) and etyl acetate4ater are added. Teaueous layer is e0tracted , times 4it t%c and te or5anic layer is bac8 e0tracted t4ice 4it

saturated sodium bicarbonate solution. Te combined aueous layers are acidified to a p* of +

4it +&D *Cl" ten e0tracted ; times 4it t%c. Te combined or5anic layers are dried(sodium sulfate) and concentrated in vacuo. Te residue is ten purified by flas


6eferencesTetraedron" 1996" 52" +,:;9-+,:',.

Tetraedron 1ett. 199"" 31"


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Te amine is dissol3ed in 4ater and sodium bicarbonate (, e) is added 4it stirrin5. Te

resultin5 solution is cooled to ' and BC anydride (+.' e) is added slo4ly as a solution inpara-dio0ane (also cooled). Te resultin5 mi0ture is stirred at & for + and allo4ed to 4arm toroom temperature o3erni5t. ?ater is ten added and te aueous layer is e0tracted , times 4it

t%c. Te or5anic layer is bac8 e0tracted t4ice 4it saturated sodium bicarbonate solution.

Te combined aueous layers are acidified to a p* of + 4it +&D *Cl" ten e0tracted ; times4it t%c. Te combined or5anic layers are dried (sodium sulfate) and concentrated in vacuo.

Te resultin5 residue can ten be purified by flas cromato5rapy (Si,) if necessary.

6emo3alTe compound is dissol3ed in +=+ trifluoroacetic acid=4ater and stirred at room temperature until

complete by T1C (usually @, ). Te solution is concentrated in vacuoand purified by flas

cromato5rapy (Si,) if necessary.6eferences

r5anic Syntesis" 1999" 76" '-


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Alloc- (allyl) carbamate


Te amine is dissol3ed in 4ater and sodium carbonate (,. e) is added 4it stirrin5. Te

resultin5 solution is cooled to ' and allyl cloroformate (+.' e) is added slo4ly as a solution inpara-dio0ane (also cooled). Te resultin5 mi0ture is stirred at & for + and allo4ed to 4arm toroom temperature o3erni5t. ?ater is ten added and te aueous layer is e0tracted , times 4it

t%c. Te or5anic layer is bac8 e0tracted t4ice 4it saturated sodium bicarbonate solution.

Te combined aueous layers are acidified to a p* of + 4it +&D *Cl" ten e0tracted ; times

4it t%c. Te combined or5anic layers are dried (sodium sulfate) and concentrated in vacuo.Te resultin5 residue can ten be purified by flas cromato5rapy (Si,) if necessary.

6emo3alTe amine is dissol3ed in dry T*F and dimetylmalonate ( e) follo4ed by

tetra8istripenylpospine palladium (&.&, e) are added at room temperature under an inert

atmospere. Te reaction is stirred until complete by T1C (usually ,2 ) and filtered. Te

solution is ten concentrated in vacuo and te resultin5 residue is purified by flascromato5rapy (Si,) if necessary.

6eferences

Tetraedron" 1996" 39" +,:;9-+,:',.Tetraedron 1ett. 1986" 23" ,'99-,


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6emo3al

Te carbamate is dissol3ed in 5lacial acetic acid=T*F +=+ and zinc dust (e0cess) is added. Te

resultin5 suspension is stirred at room temperature until complete by T1C (usually @; ). Temi0ture is ten filtered" concentrated in vacuo and redissol3ed in cloroform. Te solution is

4ased once 4it 'D aueous sodium bicarbonate" dried (sodium sulfate)" and concentrated in

vacuo. Te resultin5 residue is purified by flas cromato5rapy (Si,) if necessary.6eferences

Can. 7. Cem. 1982" 60" 9; )ten filtered and concentrated in vacuo. Te resultin5 residue is purified by flas


6eferencesTetraedron 1ett. 1966" 7" 2


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See= 7C"197!" 6"


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Perc9loric 6ci= 6=sor?e= on silic6-4el B#'l*Ci2D w6s ;oun= to ?e 6 new, 9i49ly e;;icient, ineE"ensi@e6n= reus6?le c6t6lyst ;or c9e


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;or t9e intro=uction o; 0oc 6n= A


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eeueH, ). Morris, . Newell, . Wun=erw6l=, M. Witt, J. We6@er, :. :96n4, :. :96n4, J.Org. Chem., 2&&', 71, !%*5-!%5%.

stereoconser@6ti@e "rotection 6n= =e"rotection


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T9e re6ction o; 0oc-"rotecte= ortho-6


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n e;;icient synt9esis o; NBD-0oc2-NBKD-'?H-2,3-=i6


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P=-c6t6lyHe= selecti@e oEi=6tion o; Boc-"rotecte= N-

amine protection

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