Benzoic acid, 4-fluoro-, ethyl ester → 4-[(1,1-Dimethylethyl)thio]benzoic acid

Temperature

80 °C

Ethyl 4-fluorobenzoate (1.5 g, 8.9 mmol) and tert-butylsulfanylsodium (2.0 g, 17.8 mmol) were combined in N,N-dimethylformamide (10 mL). The reaction mixture was heated to 80° C. for 2 hours. After this time, a precipitate formed and N,N-dimethylformamide (15 mL) was added and the reaction mixture was stirred for an additional 20 hours at 80° C. The reaction mixture was partitioned between ethyl acetate (100 mL) and water (100 mL). The aqueous layer was acidified with 4M hydrochloric acid, extracted with ethyl acetate (2×). The combined extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to yield 4-(tert-butylthio)benzoic acid as a colorless oil. The oil was dissolved in acetic acid (10 mL) and hydrogen peroxide (5 mL of 30% w/w, 52.0 mmol) was added to the reaction mixture. The resulting mixture was heated to 80° C. for 2 hours. The reaction mixture was then allowed to cool to room temperature, and diluted with water (50 mL) and ethyl acetate (100 mL). The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate extracts were dried over sodium sulfate, filtered, and concentrated in vacuo to yield 4-tert-butylsulfonylbenzoic acid (2.2 g, 92%) as a white solid. 1H NMR (400 MHz, DMSO) δ 13.59 (s, 1H), 8.18 (d, J=8.0 Hz, 2H), 7.94 (d, J=7.6 Hz, 2H), 1.25 (s, 9H); ESI-MS m/z calc. 242.1. found 241.3 (M−1)−; Retention time: 1.33 minutes (3 min run).

1. customAfter this time, a precipitate formed
2. customThe reaction mixture was partitioned between ethyl acetate (100 mL) and water (100 mL)
3. extractionextracted with ethyl acetate (2×)
4. dry with materialThe combined extracts were dried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo

ORD record

ord-06462a9fe85c440a8ab0d66c0afbef04

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181273B2