tert-Butanol → 96394-42-2

Temperature

2.5 °C

2-Bromoacetamide (11.1 g, 80 mmol) was suspended in ethylene dichloride (130 ml) in a 250-ml round-bottomed flask fitted with a magnetic stirrer, a thermometer, and a condenser with nitrogen flow. Oxalyl chloride (9.76 ml, 112 mmol, 1.4 eq) was added slowly to the solution at room temperature with stirring. The mixture was stirred at room temperature for 30 min, and then heated to reflux for 5 hours (the suspension became a clear solution). The condenser was replaced with a distillation system, and about 35-40 ml solvent was removed with stirring. The heating mantle was withdrawn and the reaction mixture was cooled with an ice bath to 0-5° C. A solution of tert-butanol (10.7 ml, 112 mmol, 1.4 eq) in 10 ml dichloromethane was added slowly to maintain temperature below 15° C. and the mixture was stirred at 0-15° C. for 15-30 min. The reaction mixture was diluted with dichloromethane (220 ml) and washed sequentially with aqueous saturated sodium bicarbonate solution (50 ml) and water (3×80 ml) (The amount of unreacted 2-bromoacetamide in organic layer should be controlled to <1% by 1H NMR or HPLC, otherwise, continue washing with water to meet this requirement). The combined organic layers were concentrated under reduced pressure to remove about 200-250 ml solvent (A slurry was formed). Heptane (110 ml) was added and the mixture was concentrated to remove about 50-70 ml solvent at reduced pressure. Heptane (110 ml) was added and the mixture was heated to 50° C. for 30 min, and then cooled to room temperature. The mixture was stirred at room temperature for 1 hour and filtered and washed with heptane (30 ml) to afford the desired product (15.5 g, 86%) as a white crystalline solid.

1. customfitted with a magnetic stirrer
2. stirringThe mixture was stirred at room temperature for 30 min
3. temperatureheated
4. temperatureto reflux for 5 hours (the suspension
5. customwas removed
6. stirringwith stirring
7. customThe heating mantle was withdrawn
8. temperatureto maintain temperature below 15° C.
9. stirringthe mixture was stirred at 0-15° C. for 15-30 min
10. washwashed sequentially with aqueous saturated sodium bicarbonate solution (50 ml) and water (3×80 ml) (The amount of unreacted 2-bromoacetamide in organic layer
11. washotherwise, continue washing with water
12. concentrationThe combined organic layers were concentrated under reduced pressure
13. customto remove about 200-250 ml solvent (A slurry
14. customwas formed)
15. concentrationthe mixture was concentrated
16. customto remove about 50-70 ml solvent at reduced pressure
17. additionHeptane (110 ml) was added
18. temperaturethe mixture was heated to 50° C. for 30 min
19. temperaturecooled to room temperature
20. stirringThe mixture was stirred at room temperature for 1 hour
21. filtrationfiltered
22. washwashed with heptane (30 ml)

ORD record

ord-1bbcb95dfa314789a6a70e70526c5006

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07842813B2