Water → ethyl (R)-2-tert-butoxycarbonylamino-5-(3,5-difluorophenyl)-5-oxopentanoate
Reaction equation
[CH3:1][CH2:2][O:3][C:4]([C@H:6]1[CH2:10][CH2:9][C:8](=[O:11])[N:7]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:5].O.[F:20][C:21]1[CH:22]=[C:23]([Mg]Br)[CH:24]=[C:25]([F:27])[CH:26]=1>O1CCCC1>[C:15]([O:14][C:12]([NH:7][C@H:6]([CH2:10][CH2:9][C:8]([C:23]1[CH:22]=[C:21]([F:20])[CH:26]=[C:25]([F:27])[CH:24]=1)=[O:11])[C:4]([O:3][CH2:2][CH3:1])=[O:5])=[O:13])([CH3:18])([CH3:17])[CH3:16]Participants
Procedure
To a solution of (R)-5-oxopyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (3.0 g) in tetrahydrofuran (70 mL), 3,5-difluorophenylmagnesium bromide (0.5 M solution in tetrahydrofuran; 25.7 mL) was added dropwise at −40° C. over 10 minutes, and the reaction solution was stirred at −40° C. to 0° C. for one hour. Water was added to the solution in small portions at 0° C., followed by extraction with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (heptane-ethyl acetate system) to obtain 3.0 g of the title compound as a pale yellow oil. The property values of the compound are as follows.
Workup
- extractionfollowed by extraction with ethyl acetate
- washThe extract was washed with brine
- dry with materialdried over anhydrous magnesium sulfate
- concentrationconcentrated under reduced pressure
- customThe residue was purified by silica gel column chromatography (heptane-ethyl acetate system)
Sources & evidence
- ORD record
- ord-269946eee2d24ab6b16ef013a17cfe36
- Source dataset
- uspto-grants-2011_11
- Patent number
- US08048878B2
Reaction notes
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