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With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 0 - 20℃;
22.22A Step 22A: Synthesis of (E)-methyl 2-(((benzyloxy)carbonyl)amino)-3-(3-((tert- butoxycarbonyl)amino)bicyclo[1.1.1]pentan-1-yl)acrylate (Intermediate 22A)
DBU (102 μL, 0.68 mmol) was added to a solution of tert-butyl (3-formyl bicycle [1.1.1] pentan-1-yl)carbamate (110 mg, 0.52 mmol) and methyl 2- (((benzyloxy) carbonyl)amino)-2-(dimethoxyphosphoryl)acetate (224 mg, 0.68 mmol) in DCM (3 mL) at 0°C. After stirring at rt overnight, the reaction mixture was quenched with 1 M HCl, and the two phases separated by sept cartridge. The organic layer was concentrated and the resulting crude material was purified by chromatography (EA/isohexane) to provide 144 mg (60%) Intermediate 22A. LCMS [m/z] calculated for C22H28N2O6: 416.2; found 417.3 [M+H]+, tR= 2.31min (Method 4).
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 0 - 20℃;
12.2 Step 2: methyl 2-(((benzyloxy)carbonyl)amino)-3-(oxetan-3-yl)acrylate
To the mixture d methyl 2- (((benzyloxy)carbonyl)amino)-2-(dimethoxyphosphoryl)acetate (26.0 g, 79.45 mmol, 1.0 equiv) and DBU (12 g, 79.45 mmol, 1.0 equiv) at 0oC. The mixture was slowly warmed to room temperature and stirred overnight. The mixture was concentrated and purified with column chromatography on silica gel (petroleum ether:ethyl acetate (1/1, v/v)) to give methyl 2- (((benzyloxy)carbonyl)amino)-3-(oxetan-3-yl)acrylate as a light yellow solid (4.5 g, 19 % yield for two steps). MS (ESI+) m/z 292.2 [M+H]+.
19%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 0 - 20℃;
12.2 Step 2: methyl 2-(((benzyloxy)carbonyl)amino)-3-(oxetan-3-yl)acrylate
To the mixture d methyl 2- (((benzyloxy)carbonyl)amino)-2-(dimethoxyphosphoryl)acetate (26.0 g, 79.45 mmol, 1.0 equiv) and DBU (12 g, 79.45 mmol, 1.0 equiv) at 0oC. The mixture was slowly warmed to room temperature and stirred overnight. The mixture was concentrated and purified with column chromatography on silica gel (petroleum ether:ethyl acetate (1/1, v/v)) to give methyl 2- (((benzyloxy)carbonyl)amino)-3-(oxetan-3-yl)acrylate as a light yellow solid (4.5 g, 19 % yield for two steps). MS (ESI+) m/z 292.2 [M+H]+.
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