Triethylamine → Tert-butyl 3-(3,3-difluoropyrrolidin-1-yl)azetidine-1-carboxylate
Reaction equation
Cl.[F:2][C:3]1([F:8])[CH2:7][CH2:6][NH:5][CH2:4]1.[C:9]([O:13][C:14]([N:16]1[CH2:19][C:18](=O)[CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[C:9]([O:13][C:14]([N:16]1[CH2:19][CH:18]([N:5]2[CH2:6][CH2:7][C:3]([F:8])([F:2])[CH2:4]2)[CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
A mixture of 3,3-difluoropyrrolidine hydrochloride (200 mg, 1.17 mmol), 3-oxoazetidine-1-carboxylic acid tert-butyl ester (284 mg, 1.99 mmol) and triethylamine (295 μL, 221 mg, 2.18 mmol) in DCE (10 mL) was stirred at room temperature for 1 h before the addition of sodium triacetoxyborohydride (745 mg, 3.52 mmol). The resulting mixture was stirred for 72 h then diluted with DCM and washed with H2O. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-50%) affording 3-(3,3-Difluoropyrrolidin-1-yl)azetidine-1-carboxylic acid tert-butyl ester as a colourless oil (193 mg, 63%). 1H NMR (CDCl3, 300 MHz): δ 3.95 (m, 2 H), 3.82 (dd, J=8.9, 4.9 Hz, 2 H), 3.32 (m, 1 H), 2.91 (m, 2 H), 2.82-2.63 (m, 2 H), 2.33-2.32 (m, 2 H) and 1.43 (s, 9 H).
Workup
- washwashed with H2O
- dry with materialThe organic phase was dried (Na2SO4)
- concentrationconcentrated in vacuo
- customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 0-50%)
Sources & evidence
- ORD record
- ord-d034363f7735497b81e4ec9b08400cd3
- Source dataset
- uspto-grants-2013_03
- Patent number
- US08394796B2
Reaction notes
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