反应详情

Sodium cyanoborohydride (389 mg, 6.2 mmol) was added in 8 portions to a solution of N′-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexylidene]-hydrazinecarboxylic acid tert-butyl ester (from Step 1; 1.9 g, 5.9 mmol) in 50% aqueous acetic acid, and the mixture was stirred at room temperature for 2.5 h. The mixture was cooled slightly using cold water, and then 2 M aqueous sodium hydroxide solution was added to bring the pH to approximately 7. The mixture was extracted four times with dichloromethane, and the combined extracts were washed with water and brine, then dried (sodium sulfate), filtered, evaporated, and held under high vacuum to give a gum. This was purified on a Supelco 100 g column, eluting with 0-3% methanol/dichloromethane, to give N′-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cis-cyclohexyl]-hydrazinecarboxylic acid tert-butyl ester (309 mg), N′-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-trans-cyclohexyl]-hydrazinecarboxylic acid tert-butyl ester (680 mg, 36%), and some mixed fractions. 1H NMR (300 MHz, DMSO-d6) δ 1.22 (d, 6H, J=7.0 Hz), 1.36 (s, 9H), 1.45-1.53 (m, 4H), 1.60-1.68 (m, 2H), 1.94-2.04 (m, 2H), 2.90-3.05 (m, 3H), 4.20-4.25 (m, 1H), 8.16 (br s, 1H).

1. temperatureThe mixture was cooled slightly
2. extractionThe mixture was extracted four times with dichloromethane
3. washthe combined extracts were washed with water and brine
4. dry with materialdried (sodium sulfate)
5. filtrationfiltered
6. customevaporated
7. customto give a gum
8. customThis was purified on a Supelco 100 g column
9. washeluting with 0-3% methanol/dichloromethane