Cesium carbonate → N-Cyclopropyl-4-fluoro-2-[(2S)-2-oxiranylmethoxy]benzamide
Reaction equation
[F:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=O)=[C:4]([OH:12])[CH:3]=1.[CH:13]1([NH2:16])[CH2:15][CH2:14]1.[N+](C1C=C(C=CC=1)O[CH2:24][C@@H:25]1[CH2:27][O:26]1)([O-])=O.C(=O)([O-])[O-].[Cs+].[Cs+]>>[CH:13]1([NH:16][C:6](=[O:8])[C:5]2[CH:10]=[CH:11][C:2]([F:1])=[CH:3][C:4]=2[O:12][CH2:24][C@@H:25]2[CH2:27][O:26]2)[CH2:15][CH2:14]1Participants
Procedure
A mixture of methyl 4-fluoro-2-hydroxybenzoate (0.17 g, 1 mmol) and cyclopropylamine (1 ml) was stirred at room temperature overnight. Cyclopropylamine was removed in vacuo, and the residue dissolved in dry DMF (5 ml). (2S)-2-[(3-nitrophenoxy)-methyl]oxirane (0.195 g, 1.0 mmol) and cesium carbonate (0.478 g, 1.5 mmol) were added, and the mixture was stirred at room temperature for 2 days. The reaction mixture was partitioned between ethyl acetate (50 ml) and water (50 ml). The aqueous layer was extracted with ethyl acetate (25 ml) and the combined organic layers were dried with sodium sulphate and concentrated. The residue was purified by flash chromatography (silica gel, n-heptane/ethyl acetate, 1:1) to afford the subtitle compound (0.104 g, 0.41 mmol, 41%) as a colourless solid.
Workup
- customCyclopropylamine was removed in vacuo
- dissolutionthe residue dissolved in dry DMF (5 ml)
- stirringthe mixture was stirred at room temperature for 2 days
- customThe reaction mixture was partitioned between ethyl acetate (50 ml) and water (50 ml)
- extractionThe aqueous layer was extracted with ethyl acetate (25 ml)
- dry with materialthe combined organic layers were dried with sodium sulphate
- concentrationconcentrated
- customThe residue was purified by flash chromatography (silica gel, n-heptane/ethyl acetate, 1:1)
Sources & evidence
- ORD record
- ord-72fbaf2498e44e689f2f8b842c1d9303
- Source dataset
- uspto-grants-2008_06
- Patent number
- US07388020B2
Reaction notes
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