Dimethyl Sulfoxide → ethyl rel-(1R,2S)-4-[(5-chloropyrimidin-2-yl)carbonyl]-2-methylcyclohexanecarboxylate

Temperature

-78 °C

To a solution of oxalyl chloride (0.37 mL, 3.5 mmol) in dichloromethane (4.4 mL) cooled to −78° C. was added dropwise a solution of dimethylsulfoxide (0.55 mL, 7.1 mmoL) in dichloromethane (10.8 mL). After 5 min, a solution of ethyl rel-(1R,2S)-4-[(5-chloropyrimidin-2-yl)(hydroxy)methyl]-2-methylcyclohexanecarboxylate (1 g, 3.2 mmol) in dichloromethane (6.5 mL) was added. The reaction mixture was stirred for 15 minutes at −78° C. and triethylamine (2.2 mL, 16 mmol) was added in one portion. After stirring for 10 min at −78° C., the mixture was allowed to warm to room temperature and diluted with dichloromethane (50 mL). The organic layer was successively washed with a saturated aqueous ammonium chloride solution (30 mL) and brine (2×30 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by prep-TLC (ethyl acetate/petroleum ether) to give ethyl rel-(1R,2S)-4-[(5-chloropyrimidin-2-yl)carbonyl]-2-methylcyclohexanecarboxylate. MS ESI calc'd for C15H20ClN2O3[M+H]+ 311. found 311. 1H NMR: (400 MHz, CDCl3) δ. 8.88-8.84 (m, 2H), 4.17-4.10 (m, 2H), 2.71-2.48 (m, 2H), 2.14-2.01 (m, 1H), 1.90-1.73 (m, 5H), 1.53-1.41 (m, 1H), 1.28-1.24 (m, 3H), 1.06-0.99 (m, 3H).

1. stirringAfter stirring for 10 min at −78° C.
2. temperatureto warm to room temperature
3. washThe organic layer was successively washed with a saturated aqueous ammonium chloride solution (30 mL) and brine (2×30 mL)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by prep-TLC (ethyl acetate/petroleum ether)

ORD record

ord-3f15bd7bb2a54ba88b339967a4ef9586

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09416111B2