Acetone → 1-(4-Benzyloxycarbonylamino-phenyl)-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester

HRID 1400023Notes

Reaction equation

HRID 1400023 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[C:10]([C:14]3[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=3)([CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)=O.C(=O)(O)[O-].[Na+].Cl[C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32]>O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]2[C:10]([C:14]3[CH:19]=[CH:18][C:17]([NH:20][C:31]([O:33][CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[O:32])=[CH:16][CH:15]=3)([CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 180AcetoneHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 67509408Tert-butyl 1-(4-aminophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate

Product 1

HCID 675082321-(4-Benzyloxycarbonylamino-phenyl)-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl esterYield 92%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1-(4-amino-phenyl)-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (1.5 g, 5.5 mmol), in 1:1 acetone:water (12 mL) was added sodium bicarbonate (1.2 g, 13.7 mmol). The resulting solution was cooled to 0° C. and benzyl chloroformate (2.8 mL, 8.2 mmol, 50% solution in toluene) was added dropwise. The reaction mixture was stirred at r.t. and progress of the reaction was monitored by TLC. On completion, solvent was evaporated under reduced pressure and the residue was dissolved in ethyl acetate (50 mL). The organic layer was washed with water (2×10 mL), brine (10 mL), dried over anhydrous sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography (silica gel, 5:5 EtOAc:Pet. ether) to provide the title compound (2.05 g, 92%) as off white solid.

Workup

  1. customOn completion, solvent was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in ethyl acetate (50 mL)
  3. washThe organic layer was washed with water (2×10 mL), brine (10 mL)
  4. dry with materialdried over anhydrous sodium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (silica gel, 5:5 EtOAc:Pet. ether)

Sources & evidence

ORD record
ord-f3edfd5d27d645119c8f736bf73efc65
Source dataset
uspto-grants-2014_12
Patent number
US08906913B2

Reaction notes

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