Dimethylformamide → HCID 55206438, compound
Reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][OH:6].F[C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]=1[C:17]([F:20])([F:19])[F:18].[H-].[Na+].CN(C=O)C>C1COCC1>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][O:6][C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]=1[C:17]([F:18])([F:20])[F:19]Participants
Procedure
3-Methoxypropan-1-ol (217 mg, 2.40 mmol), 4-fluoro-3-(trifluoromethyl)benzoic acid (500 mg, 2.40 mmol), and NaH (240 mg, 6.0 mmol) were combined in THF (10 mL) and DMF (1 mL) at 0° C. under an atmosphere of nitrogen. The reaction mixture was stirred for 16 h at room temperature. The reaction mixture was partitioned between ethyl acetate and a 1M aqueous solution of hydrochloric acid. The layers were separated and then the organic layer was washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, and evaporated to dryness. The crude material was purified by column chromatography utilizing a gradient of 0-5% methanol in dichloromethane to yield 4-(3-methoxypropoxy)-3-(trifluoromethyl)benzoic acid (213 mg, 32%) as a white solid. ESI-MS m/z calc. 278.1. found 279.3 (M+1)+; Retention time: 1.38 minutes (3 min run). 4-Propoxy-3-(trifluoromethyl)benzoic acid was prepared from 4-fluoro-3-(trifluoromethyl)benzoic acid and 3-fluoro-4-(2-methoxyethoxy)benzoic acid was prepared from 3,4-difluorobenzoic acid using the procedure described above.
Workup
- customat 0° C.
- customThe reaction mixture was partitioned between ethyl acetate
- customThe layers were separated
- washthe organic layer was washed with a saturated aqueous solution of sodium chloride
- dry with materialdried over sodium sulfate
- customevaporated to dryness
- customThe crude material was purified by column chromatography
Sources & evidence
- ORD record
- ord-fea184e2b54e40e79e85531accfed537
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08598164B2
Reaction notes
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