Water → (R)-tert-Butyl (1-(4-fluorobenzyl)pyrrolidin-3-yl)carbamate

HRID 226340Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:13][CH2:12][NH:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:14][C:15]1[CH:23]=[CH:22][C:18]([C:19](Cl)=O)=[CH:17][CH:16]=1.C(N(CC)C(C)C)(C)C.O>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]1[CH2:13][CH2:12][N:11]([CH2:19][C:18]2[CH:22]=[CH:23][C:15]([F:14])=[CH:16][CH:17]=2)[CH2:10]1)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of (3R)-(+)-3-(tert-butoxycarbonylamino)pyrrolidine (5.0 g) in DMF (50 ml) was added 4-fluorobenzoylchloride (3.38 ml) and N,N-diisopropylethylamine (9.35 ml), the mixture was stirred at 70° C. for 2 hours. The mixed solution was poured into a mixture of water (300 ml) and AcOEt (300 ml). The organic layer was separated, washed with water twice and brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with 5% MeOH in dichloromethane to give [1-(4-fluoro-benzyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (6.8 g). To a solution of [1-(4-fluoro-benzyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (6.8 g) in MeOH(34 ml) was treated with 4N HCl in AcOEt (29 ml) and was stirred at 25° C. for 12 hours. The solvent was removed under reduced pressure. Recrystallization (acetonitrile-MeOH) provided (3R)-1-(4-fluorobenzyl)-3-pyrrolidinamine dihydrochloride as white solid (3.77 g).

Workup

customThe organic layer was separated
washwashed with water twice
dry with materialbrine, dried over sodium sulfate
concentrationconcentrated in vacuo
customThe residue was purified by silica gel column chromatography
washeluted with 5% MeOH in dichloromethane

Sources & evidence

ORD record: ord-95d217c31e3c4069bdcf7e8207724daf
Source dataset: uspto-grants-2009_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07557127B2

Reaction notes

Loading…