Cesium carbonate → HCID 86703588, compound
Reaction equation
[C@@H:1]12[CH2:7][C@@H:4]([CH2:5][CH2:6]1)[CH2:3][C@@H:2]2[OH:8].[Cl:9][C:10]1[C:11](F)=[CH:12][C:13]([F:23])=[C:14]([CH:22]=1)[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.C(OCC)(=O)C>[C@@H:1]12[CH2:7][C@@H:4]([CH2:5][CH2:6]1)[CH2:3][C@@H:2]2[O:8][C:11]1[C:10]([Cl:9])=[CH:22][C:14]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])=[C:13]([F:23])[CH:12]=1Participants
Conditions
- Temperature
- 80 °C
Procedure
A mixture of (1S,2S,4R)-bicyclo[2.2.1]heptan-2-ol (1.0 g, 8.92 mmol), tert-butyl 5-chloro-2,4-difluorobenzoate (2.88 g, 11.60 mmol), and cesium carbonate (5.81 g, 17.84 mmol) in anhydrous dimethylsulfoxide (12 mL) was heated in a sealed tube at 80° C. for 18 hours, then at 115° C. for 1 hour. The reaction mixture was cooled to ambient temperature and diluted with ethyl acetate (80 mL), washed with water (30 mL), saturated ammonium chloride (40 mL) and brine (40 mL); dried over anhydrous sodium sulfate; filtered and concentrated in vacuo. The residue was triturated with methanol to provide the title compound (0.76 g, 25%): 1H NMR (300 MHz, CDCl3) δ 7.84 (d, J=7.5 Hz, 1H), 6.57 (d, J=12.4 Hz, 1H), 4.22-4.17 (m, 1H), 2.51-2.46 (m, 1H), 2.38-2.31 (m, 1H), 1.83-1.67 (m, 2H), 1.66-1.58 (m, 1H), 1.56 (s, 9H), 1.52-1.42 (m, 2H), 1.26-1.09 (m, 3H); MS (ES+) m/z 285.0, 287.0 (M-55).
Workup
- temperatureThe reaction mixture was cooled to ambient temperature
- washwashed with water (30 mL), saturated ammonium chloride (40 mL) and brine (40 mL)
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue was triturated with methanol
Sources & evidence
- ORD record
- ord-720953c6cc9c40b49886e7be43dd9def
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08952169B2
Reaction notes
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