Aluminium lithium hydride → tert-butyl N-[2-(3,5-difluorophenyl)-1-oxopropan-2-yl]carbamate
Reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=1)([CH3:17])[C:10](OC(C)(C)C)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]([C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=1)([CH3:17])[CH:10]=[O:11])([CH3:2])([CH3:3])[CH3:4]Participants
4
Conditions
- Temperature
- -78 °C
Procedure
To a stirred solution of tert-butyl 2-[(tert-butoxycarbonyl)amino]-2-(3,5-difluorophenyl)propanoate (27.0 g, 76 mmol) in THF (350 mL) at −78° C. was added LiAlH4 (76 mL of a 1 M solution in THF, 76 mmol), dropwise. The reaction mixture was stirred at −78° C. for 3 h, then quenched with EtOAc (76 mL), then H2O (228 mL), then 1 N aqueous NaOH (76 mL), then EtOAc (228 mL). The reaction mixture was warmed to ambient temperature, stirred for 1 h, filtered, and extracted with EtOAc (2×450 mL). The organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with hexane:EtOAc—100:0 to 70:30, to give the title compound. MS: m/z=186 (M−CO2C4H7).
Workup
- customquenched with EtOAc (76 mL)
- temperatureThe reaction mixture was warmed to ambient temperature
- stirringstirred for 1 h
- filtrationfiltered
- extractionextracted with EtOAc (2×450 mL)
- dry with materialThe organic extracts were dried over Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude product was purified by silica gel chromatography
- washeluting with hexane
Sources & evidence
- ORD record
- ord-047f63c27e534fdb85cf8d8e4e857448
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08765759B2
Reaction notes
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