5-Chloro-2,4-difluorobenzoic acid → 5-Chloro-2-fluoro-4-((3,5,7-trifluoroadamantan-1-yl)methoxy)benzoic acid

A mixture of (3,5,7-trifluoroadamantan-1-yl)methanol (1.37 g, 6.22 mmol) and potassium tert-butoxide (0.91 g, 8.09 mmol) in anhydrous dimethylsulfoxide (20 mL) was stirred under nitrogen for 20 minutes. The reaction mixture was treated with a mixture of 5-chloro-2,4-difluorobenzoic acid (1.20 g, 6.22 mmol) and potassium tert-butoxide (0.70 g, 6.22 mmol) in anhydrous dimethylsulfoxide (10 mL) that had been stirred for 10 min. The resulting mixture was stirred under nitrogen at ambient temperature for 20 hours, diluted with ethyl acetate (120 mL), water (20 mL) and 1 M aqueous hydrochloric acid solution (50 mL). The separated organic layer was washed with 1 M aqueous hydrochloric acid solution (50 mL) and brine; dried over anhydrous sodium sulfate; filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (2:1 hexanes:ethyl acetate (+0.2% acetic acid v/v)) to provide the title compound (0.98 g, 40%): 1H NMR (300 MHz, DMSO-d6) δ 13.13 (br s, 1H), 7.83 (d, J=7.6 Hz, 1H), 7.18 (d, J=12.6 Hz, 1H), 4.00 (s, 2H), 2.25-2.14 (m, 3H), 2.06-1.96 (m, 3H), 1.81-1.73 (m, 6H); MS (ES−) m/z 391.2, 393.2 (M−1).

1. stirringhad been stirred for 10 min
2. stirringThe resulting mixture was stirred under nitrogen at ambient temperature for 20 hours
3. washThe separated organic layer was washed with 1 M aqueous hydrochloric acid solution (50 mL) and brine
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe residue was purified by silica gel column chromatography (2:1 hexanes

ORD record

ord-2cd9527a4af84d8180109aae0ff44fe8

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952169B2