反应详情

A solution of 2-methyl-propane-2-sulfinic acid [1-(8-cyclopropylmethyl-1,4-dioxa-spiro[4.5]dec-8-yl)-2,2,2-trifluoro-ethyl]-amide (20, 1.00 g, 2.52 mmol) in 80% acetic acid (10 mL) was heated in a microwave oven for 10 min at 130° C. Then, the reaction mixture was slowly dropped into cold saturated sodium bicarbonate solution (150 mL), stirred for 30 min at room temperature and extracted three times with dichloromethane. The combined organic layers were dried over magnesium sulphate, filtered, and concentrated in vacuo to give the crude ketone, which was taken up in ethanol (20 mL), cooled to 0° C. and treated with sodium borohydride (190 mg, 5.03 mmol, 2.0 eq.). After the reaction went to completion, the mixture was poured onto water (20 mL) and extracted three times with dichloromethane. The organic layers were concentrated in vacuo and the residue was dissolved in a mixture of 2-propanol (15 mL) and 6N aqueous hydrochloric acid (5 mL). After stirring overnight at room temperature, another 5 mL of 6N aqueous hydrochloric acid were added and the mixture was warmed to 50° C. for 1 h. The reaction mixture was concentrated in vacuo and lyophilized twice from water to give the title compound (21) as racemic mixture of diastereoisomers as its hydrochloride. Rt=0.73 min, 0.82 min (Method B). Detected mass: 252.3 (M+H+).

1. extractionextracted three times with dichloromethane
2. dry with materialThe combined organic layers were dried over magnesium sulphate
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customto give the crude ketone, which
6. temperaturecooled to 0° C.
7. additionthe mixture was poured onto water (20 mL)
8. extractionextracted three times with dichloromethane
9. concentrationThe organic layers were concentrated in vacuo
10. dissolutionthe residue was dissolved in a mixture of 2-propanol (15 mL) and 6N aqueous hydrochloric acid (5 mL)
11. stirringAfter stirring overnight at room temperature
12. additionanother 5 mL of 6N aqueous hydrochloric acid were added
13. temperaturethe mixture was warmed to 50° C. for 1 h
14. concentrationThe reaction mixture was concentrated in vacuo