Sodium Hydroxide → tert-butyl (1R,2R)-1-(2-bromo-5-fluoropyridin-4-yl)-2-(2-fluorophenyl)-2-hydroxyethylcarbamate

Temperature

0 °C

To tert-butyl carbamate (150 mg, 1.28 mmol) in n-propanol (1.75 mL) was added sodium hydroxide (49.8 mg, 1.25 mmol) in water (3.5 mL) followed by tert-butyl hypochlorite (0.141 mL, 1.246 mmol). After 5 min, the solution was cooled to 0° C. and treated with a solution of DHQD2(PHAL) (16.57 mg, 0.021 mmol) in n-propanol (1.75 mL). The reaction was diluted with n-propanol (3.5 mL) and treated with (E)-2-bromo-5-fluoro-4-(2-fluorostyryl)pyridine (90 mg, 0.304 mmol) as a solid in one portion. To this was added potassium osmate dihydrate (5.60 mg, 0.015 mmol) as a solid in one portion. The reaction was allowed to gradually warm to room temperature in the dewar overnight. The reaction was cooled to 0° C. and quenched by addition of sodium thiosulfate (150 mg) in water (3 mL). The ice bath was removed and stirring continued for 30 min. The reaction was diluted with ether, washed with water (3×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (25% EtOAc/Hex) gave 93 mg (36%) as a foam solid. Mass spec.: 429.1 (MH)+.

1. temperatureto gradually warm to room temperature in the dewar overnight
2. temperatureThe reaction was cooled to 0° C.
3. customquenched by addition of sodium thiosulfate (150 mg) in water (3 mL)
4. customThe ice bath was removed
5. waitcontinued for 30 min
6. additionThe reaction was diluted with ether
7. washwashed with water (3×)
8. dry with materialbrine, dried over magnesium sulfate
9. concentrationconcentrated
10. customColumn chromatography (25% EtOAc/Hex) gave 93 mg (36%) as a foam solid

ORD record

ord-3416f59afcf54cf2932d0a5a4135c8ed

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691821B2