Benzyl chloroformate → (2S)-Methyl-1-(benzyloxycarbonyl)azetidine-2-carboxylate

HRID 1264479Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

(2S)-Methyl azetidine-2-carboxylate (2.83 g, 18.7 mmol, 1.0 eq) was dissolved in dry dichloromethane (100 mL) and cooled to about 0° C. under an argon atmosphere. After the addition of benzyl chloroformate (3.00 mL, 20.0 mmol, 1.1 eq), diisopropyl ethylamine (8.00 mL, 45.9 mmol, 2.5 eq) was added to the mixture dropwise. The reaction mixture was stirred at about 0° C. for about 30 minutes and then at about room temperature overnight. The solvent was evaporated and then the residue was dissolved in ether, washed with 1N HCl, water and brine, dried over magnesium sulfate and concentrated. Flash chromatography (in ether) gave 3.75 g (80% yield) of the product as a colorless oil. 1H NMR (CDCl3) δ 2.19-2.32 (m, 1H); 2.52-2.66 (m, 1H); 3.74 (s, 3H); 3.94-4.03 (m, 1H); 4.08-4.18 (m, 1H); 4.72 (dd, 1H, J=9.4, 6.9); 5.12 (q, 2H, J=12.9); 7.29-7.42 (m, 5H).

Workup

additionwas added to the mixture dropwise
customat about room temperature
customovernight
customThe solvent was evaporated
dissolutionthe residue was dissolved in ether
washwashed with 1N HCl, water and brine
dry with materialdried over magnesium sulfate
concentrationconcentrated

Sources & evidence

ORD record: ord-aab4cef257de47a1a892227227c9ec70
Source dataset: uspto-grants-2003_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06544976B1

Reaction notes

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