tert-Butanol → HCID 72213060, compound
Reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([C:8]2(C(O)=O)[CH2:10][CH2:9]2)[CH:5]=[CH:4][N:3]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:21])C=CC=CC=1.C([N:33]([CH2:36]C)CC)C.[C:38]([OH:42])([CH3:41])([CH3:40])[CH3:39]>>[C:38]([O:42][C:36](=[O:21])[NH:33][C:8]1([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Br:1])[CH:7]=2)[CH2:9][CH2:10]1)([CH3:41])([CH3:40])[CH3:39]Participants
Conditions
- Temperature
- 90 °C
Procedure
To a solution of crude 1-(2-bromo-pyridin-4-yl)-cyclopropanecarboxylic acid (0.350 g, 1.45 mmol) in tert-butanol (7 mL) in a pressure vessel is added diphenylphosphoryl azide (0.312 mL, 1.45 mmol) and triethylamine (0.202 mL, 1.45 mmol). The tube is sealed and the reaction mixture is stirred at 90° C. After 4 hours, the pressure vessel is cooled in an ice-bath, vented and opened. The reaction mixture is concentrated in vacuo. The resulting residue is dissolved in ethyl acetate (70 mL), washed with saturated aqueous ammonium chloride (70 mL) and saturated aqueous sodium bicarbonate (70 mL), dried over MgSO4, filtered and concentrated. The residue is purified by silica gel chromatography eluting with a gradient of 0-50% ethyl acetate in heptane to afford [1-(2-bromo-pyridin-4-yl)-cyclopropyl]-carbamic acid tert-butyl ester.
Workup
- customThe tube is sealed
- temperaturethe pressure vessel is cooled in an ice-bath
- concentrationThe reaction mixture is concentrated in vacuo
- dissolutionThe resulting residue is dissolved in ethyl acetate (70 mL)
- washwashed with saturated aqueous ammonium chloride (70 mL) and saturated aqueous sodium bicarbonate (70 mL)
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated
- customThe residue is purified by silica gel chromatography
- washeluting with a gradient of 0-50% ethyl acetate in heptane
Sources & evidence
- ORD record
- ord-b17e8a26b0e14f30b471fe8e829b2770
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09056858B2
Reaction notes
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