Trimethylamine → 1-benzyl-3-(BOC-amino)-3-trifluoromethylpyrrolidine

Reaction equation

[CH2:1]([N:8]1[CH2:12][CH2:11][C:10]([C:16]([F:19])([F:18])[F:17])(C(O)=O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:27])C=CC=CC=1.C[N:38]([CH3:40])C.[C:41]([OH:45])([CH3:44])([CH3:43])[CH3:42]>>[CH2:1]([N:8]1[CH2:12][CH2:11][C:10]([NH:38][C:40]([O:45][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:27])([C:16]([F:17])([F:18])[F:19])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Reactant 4

HCID 1146Trimethylamine

HCID 6386tert-Butanol

HCID 199401P,P-Diphenylphosphinic azide

HCID 196913671-Benzyl-3-(trifluoromethyl)pyrrolidine-3-carboxylic acid

Product 1

HCID 196914881-benzyl-3-(BOC-amino)-3-trifluoromethylpyrrolidineYield 96.7%

Procedure

A mixture of 1.42 g of the compound from step 454a, 1.71 g of diphenylphosphoryl azide, 12.3 g of t-butanol and 0.627 g of trimethyl amine was heated at reflux under N2 for 24 hours. The mixture was concentrated to dryness, and the residue was dissolved in methylene chloride. The solution was washed with satd. NaHCO3 and water, then concentrated. The residue was chromatographed on silica gel to give 1.73 g of the title compound.