Hydrochloric Acid → HCID 86703556, compound
Reaction equation
[CH3:1][C:2]1([CH2:12][OH:13])[CH2:11][CH2:10][C:5]2([O:9][CH2:8][CH2:7][O:6]2)[CH2:4][CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:20][C:21]1[C:22](F)=[CH:23][C:24]([F:34])=[C:25]([CH:33]=1)[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].Cl>CS(C)=O>[Cl:20][C:21]1[C:22]([O:13][CH2:12][C:2]2([CH3:1])[CH2:11][CH2:10][C:5]3([O:6][CH2:7][CH2:8][O:9]3)[CH2:4][CH2:3]2)=[CH:23][C:24]([F:34])=[C:25]([CH:33]=1)[C:26]([O:28][C:29]([CH3:30])([CH3:31])[CH3:32])=[O:27]Participants
Conditions
- Temperature
- 70 °C
Procedure
To a solution of (8-methyl-1,4-dioxaspiro[4.5]decan-8-yl)methanol (0.301 g, 1.65 mmol) in anhydrous dimethylsulfoxide (3 mL) were added cesium carbonate (1.07 g, 3.30 mmol) and tert-butyl 5-chloro-2,4-difluorobenzoate (0.37 g, 1.49 mmol) and the reaction mixture was stirred at 70° C. for 16 hours. The reaction mixture was cooled down to room temperature and acidified to pH=1 with 5% aqueous hydrochloric acid solution and extracted with diethyl ether (2×15 mL). The combined organic layers were washed with brine (15 mL); dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Purification of the residue by column chromatography (0 to 10% ethyl acetate in hexanes) afforded the title compound (0.28 g, 45%). 1H NMR (300 MHz, CDCl3) δ 7.85 (d, J=7.67 Hz, 1H), 6.60 (d, J=12.13 Hz, 1H), 3.96-3.89 (m, 4H), 3.72 (s, 1H), 1.98-1.37 (m, 17H), 1.12 (s, 1H).
Workup
- temperatureThe reaction mixture was cooled down to room temperature
- extractionextracted with diethyl ether (2×15 mL)
- washThe combined organic layers were washed with brine (15 mL)
- dry with materialdried over anhydrous sodium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customPurification of the residue by column chromatography (0 to 10% ethyl acetate in hexanes)
Sources & evidence
- ORD record
- ord-c848a7c0541e4137bf9dfdb5fe6e1c4e
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08952169B2
Reaction notes
Loading…