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 the crude 1-(2-bromopyridin-4-yl)-cyclopropanecarboxylic acid (350 mg, 1.45 mmol) in t-butanol (7 mL) is added diphenylphosphoryl azide (0.312 mL, 1.45 mmol) and triethylamine (0.202 mL, 1.45 mmol) in a pressure vessel. The tube is sealed and the reaction mixture is warmed 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 EtOAc (70 mL), washed with saturated aqueous ammonium chloride (70 mL), 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% EtOAc in heptane to afford [1-(2-bromopyridin-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 EtOAc (70 mL)
- washwashed with saturated aqueous ammonium chloride (70 mL), 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% EtOAc in heptane
Sources & evidence
- ORD record
- ord-d3b9687bcb8c467785f9422ef35f7b68
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08927550B2
Reaction notes
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