Tetrahydrofuran → 2-[(S)-1-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethoxy]-N-(2,2,3,3,3-pentafluoropropyl)acetamide

Temperature

-15 °C

Under a nitrogen atmosphere, a solution of sodium hexamethyldisilazide in tetrahydrofuran (1.1 M, 5.31 ml, 5.84 mmol) was cooled to −15° C., and a solution of (S)-1-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethanol (Compound 5: 633.7 mg, 2.337 mmol) in dimethylformamide (1 ml) was added thereto over 4 minutes. The resulting mixture was stirred at −15° C. for 7 minutes, and a solution of 2-bromo-N-(2,2,3,3,3-pentafluoropropyl)acetamide (726 mg, 2.688 mmol) in dimethylformamide (1 ml) was added thereto over 5 minutes. After stirring the reaction solution at −5° C. for 30 minutes, aqueous ammonium chloride solution (5 ml) and hexane (20 ml) were added thereto, and the separation of the solution was conducted. The obtained organic layer was sequentially washed with water (5 ml) and saturated brine (4 ml)/water (1 ml), and the solvent was evaporated. The obtained crude product was purified by silica gel column chromatography to obtain 2-[(S)-1-{(3aS,7E,7aR)-7-(bromomethylene)-3a,4,5,6,7,7a-hexahydro-3a-methyl-1H-indene-3-yl}ethoxy]-N-(2,2,3,3,3-pentafluoropropyl)acetamide (1.08 g, quantitatively).

1. waitover 5 minutes
2. stirringAfter stirring the reaction solution at −5° C. for 30 minutes
3. customthe separation of the solution
4. washThe obtained organic layer was sequentially washed with water (5 ml) and saturated brine (4 ml)/water (1 ml)
5. customthe solvent was evaporated
6. customThe obtained crude product
7. customwas purified by silica gel column chromatography

ORD record

ord-89a0867db7f64800aea355d36476c984

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08173824B2