반응 #89777

반응 방정식

4-methylmorpholine

acetyl chloride

1-tert-butyl 2-methyl(1S,2S,4R)-4-(piperidin-4-yloxy)cyclohexane-1,2-dicarboxylate hydrochloride

→

1-tert-butyl 2-methyl(1S,2S,4R)-4-[(1-acetylpiperidin-4-yl)oxy]cyclohexane-1,2-dicarboxylate

용매

acetonitrile

ACN

반응 조건

후처리

1. 1
   기타quenched with Water
2. 2
   추출extracted with EA
3. 3
   농축concentrated

실험 절차

A solution of acetyl chloride (24 uL, 0.00033 mol) in 0.5 ml of ACN was added to a solution of 1-tert-butyl 2-methyl(1S,2S,4R)-4-(piperidin-4-yloxy)cyclohexane-1,2-dicarboxylate hydrochloride made above (50 mg, 0.0001 mol) and 4-methylmorpholine (44 uL, 0.00040 mol) in acetonitrile (1.5 mL, 0.029 mol) at 22 Celsius. It was stirred at rt for 30 min, then quenched with Water, extracted with EA, and concentrated to give 1-tert-butyl 2-methyl(1S,2S,4R)-4-[(1-acetylpiperidin-4-yl)oxy]cyclohexane-1,2-dicarboxylate. 2 ml of TFA was added in 1-tert-butyl 2-methyl(1S,2S,4R)-4-[(1-acetylpiperidin-4-yl)oxy]cyclohexane-1,2-dicarboxylate (0.1 mmol, 0.0001 mol) in dichloromethane (2 ml). It was stirred at rt overnight and concentrated to give the corresponding TFA salt for next step. Benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate (49 mg, 0.00011 mol) was added To a solution of (1S,2S,4R)-4-[(1-acetylpiperidin-4-yl)oxy]-2-(methoxycarbonyl)cyclohexanecarboxylic acid made above (0.1 mmol, 0.0001 mol) and 1-phenylpiperazine (17 uL, 0.00011 mol) in N,N-dimethylformamide (0.5 mL, 0.006 mol) at rt. After 5 min, N,N-diisopropylethylamine (52 uL, 0.00030 mol) was added at 0 Celsius. It was stirred at rt overnight. The reaction was chromatographed by combiflash (ethyl acetate in hexanes: 100%).

출처