Benzyl chloroformate → Ethyl 1-(((benzyloxy)carbonyl)amino)cyclopropanecarboxylate

HRID 246707

Reaction equation

HRID 246707 reaction equation
Cl.[NH2:2][C:3]1([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:5][CH2:4]1.C([O-])(O)=O.[Na+].Cl[C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18]>C(OCC)(=O)C.O>[CH2:20]([O:19][C:17]([NH:2][C:3]1([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:5][CH2:4]1)=[O:18])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 386203Ethyl 1-aminocyclopropane-1-carboxylate hydrochlorideHCID 516892Sodium Bicarbonate

Product 1

HCID 13134749Ethyl 1-(((benzyloxy)carbonyl)amino)cyclopropanecarboxylateYield 91%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of ethyl 1-aminocyclopropanecarboxylate hydrochloride (9.5 g, 57.3 mmol) in 450 mL of ethyl acetate was cooled to 0° C., a solution of NaHCO3 (39.5 g, 470.3 mmol) in 325 mL of water was added slowly. Then benzyl chloroformate (13.3 g, 78.2 mmol) was added drop-wise. The cold bath was removed and the mixture was stirred at room temperature for 16 hours. The organic phase was washed with 1N HCl (100 mL), saturated NaHCO3 solution (100 mL), brine (100 mL), and dried over anhydrous sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated to give a white solid. The solid was purified by column chromatography (silica gel, 200-300 mesh, eluting with a mixture of ethyl acetate and petroleum ether (1:3, v/v) to give ethyl 1-(benzyloxycarbonylamino)cyclopropanecarboxylate (13.7 g, 91%) as a white solid. MS: (M+H)+=286.1; 1H NMR (300 MHz, CDCl3): δ 7.37-7.32 (m, 5H), 5.13 (s, 2H), 4.70 (s, 1H), 4.13 (brs, 2H), 1.59-1.53 (m, 2H), 1.23-1.19 (m, 5H).

Workup

  1. customThe cold bath was removed
  2. washThe organic phase was washed with 1N HCl (100 mL), saturated NaHCO3 solution (100 mL), brine (100 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe drying agent was removed by filtration
  5. concentrationthe filtrate was concentrated
  6. customto give a white solid
  7. customThe solid was purified by column chromatography (silica gel, 200-300 mesh
  8. washeluting with a mixture of ethyl acetate and petroleum ether (1:3

Sources & evidence

ORD record
ord-04b0d670ab73489eaffc94edfd1fae0a
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Linked notes

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