Hydrochloric Acid → tert-butyl [(1R,2S)-2-ethenyl-1-{[(1-methylcyclopropyl)sulfonyl]carbamoyl}cyclopropyl]carbamate

Temperature

85 °C

A round-bottom flask was charged with the carboxylic acid product of step 1 (2 g, 8.80 mmol) and 1,1′-carbonyldiimidazole (2.141 g, 13.20 mmol). Dry THF (44.0 ml) was added under anhydrous conditions and the mixture was heated (oil bath at 85° C.) for 2 hours with exclusion of moisture. The mixture was cooled to room temp and a solution of 1-methylcyclopropane-1-sulfonamide (2.379 g, 17.60 mmol) in dry THF (10 mL) was added followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (2.63 ml, 17.60 mmol). The mixture was heated (oil bath at 75° C.) overnight. The reaction mixture was treated with aq 1M HCl (20 mL) and water (50 mL). The product was extracted into ethyl acetate (400 mL) Upon separation, the organic layer was washed with aq 1M HCl/water (1:2, 80 mL), and brine (80 mL), dried over magnesium sulfate, filtered and concentrated in rotavap. The residue was purified on a gold cap RediSep® (120 g) silica gel column (gradient: 0 to 25% ethyl acetate in dichloromethane) to give the title compound (2.25 g, 6.53 mmol, 74.2% yield) as a white powder.

1. temperatureThe mixture was cooled to room temp
2. temperatureThe mixture was heated (oil bath at 75° C.) overnight
3. extractionThe product was extracted into ethyl acetate (400 mL) Upon separation
4. washthe organic layer was washed with aq 1M HCl/water (1:2, 80 mL), and brine (80 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in rotavap
8. customThe residue was purified on a gold
9. customcap RediSep® (120 g) silica gel column (gradient: 0 to 25% ethyl acetate in dichloromethane)

ORD record

ord-0e967e7a8dc24e399fe6525ff6e2c171

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09328138B2