Tetrahydrofuran → HCID 86588456, compound
Reaction equation
[O:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C([Li])CCC.COCN[C:15]([CH:17]1[CH2:21][C:20](=O)[N:19]([C@H:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH3:24])[CH2:18]1)=[O:16].[O:31]1CCCC1>>[O:1]1[CH:5]=[C:4]([C:15]([CH:17]2[CH2:21][CH2:20][N:19]([C@H:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH3:24])[C:18]2=[O:31])=[O:16])[N:3]=[CH:2]1Participants
Conditions
- Temperature
- -78 °C
Procedure
To a cooled solution (−78° C.) of oxazole (10.3 g, 149.1 mmol) in tetrahydrofuran (150 mL) was added n-butyl lithium (2.5 M in hexane, 53.7 mL, 134.2 mmol). The solution was stirred at −78° C. for three hours. To the cold solution was added a solution of 5-oxo-1-((S)-1-phenylethyl)pyrrolidine-3-carboxylic acid, methoxymethylamide (8.2 g, 29.8 mmol [WO 0031062]) in tetrahydrofuran (50 mL). The mixture was warmed to ambient temperature and allowed to stir three hours followed by treatment with water, saturated aqueous ammonium chloride, and extraction with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and the solvent removed under reduced pressure. The resulting residue was purified by silica gel column chromatography, eluting with hexane:ethyl acetate (1:4) to obtain 1.96 g of the title compound as a 1:1 mixture of isomers.
Workup
- temperatureThe mixture was warmed to ambient temperature
- stirringto stir three hours
- extractionfollowed by treatment with water, saturated aqueous ammonium chloride, and extraction with ethyl acetate
- dry with materialThe combined organic layers were dried over sodium sulfate
- filtrationfiltered
- customthe solvent removed under reduced pressure
- customThe resulting residue was purified by silica gel column chromatography
- washeluting with hexane:ethyl acetate (1:4)
Sources & evidence
- ORD record
- ord-aa337ad3d70b4ea9ae75f6df1aa6aa31
- Source dataset
- uspto-grants-2005_03
- Patent number
- US06864259B2
Reaction notes
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