Ethyl Acetate → (1S,5R)-5-Fluoromethyl-2-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.2.0]heptane-1-carboxylic acid methyl ester
Reaction equation
COCCN(S(F)(F)[F:11])CCOC.[CH3:14][O:15][C:16]([C@@:18]12[CH2:24][CH2:23][C@:22]1([CH2:25]O)[CH2:21][N:20]([C@@H:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH3:28])[C:19]2=[O:35])=[O:17].C(=O)(O)[O-].[Na+].C(OCC)(=O)C>ClCCl.O>[CH3:14][O:15][C:16]([C@@:18]12[CH2:24][CH2:23][C@:22]1([CH2:25][F:11])[CH2:21][N:20]([C@@H:27]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH3:28])[C:19]2=[O:35])=[O:17]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 50 °C
Procedure
Bis(2-methoxyethyl)aminosulfur trifluoride (1.98 mL, 10.7 mmol) was added to a solution of (1S,5R)-5-hydroxymethyl-2-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.2.0]heptane-1-carboxylic acid methyl ester (1.30 g, 4.30 mmol) in dichloromethane in a nitrogen atmosphere at room temperature. The mixture was heated to 50° C. and stirred for 12 hours. Then, a saturated sodium bicarbonate solution (10 mL) was added, and the mixture was stirred for 10 minutes. The reaction solution was poured into a mixture of ethyl acetate (50 mL) and water (30 mL), followed by extraction with ethyl acetate (200 mL). After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1→2:1→1.5:1) to give 1.26 g (96%) of the title compound as a pale yellow oil.
Workup
- stirringthe mixture was stirred for 10 minutes
- extractionfollowed by extraction with ethyl acetate (200 mL)
- filtrationAfter filtration
- concentrationthe filtrate was concentrated under reduced pressure
- customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=3:1→2:1→1.5:1)
Sources & evidence
- ORD record
- ord-9dfcbd314290482b80a4aabb5023ba22
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08618094B2
Reaction notes
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