反应详情

To a stirred solution of [(R)-1-(N-Benzyl-carbamimidoyl)-2-methyl-propyl]-carbamic acid t-butyl ester (16.37 g, 53.6 mMol) in CH2Cl2 (150 mL) with cooling at 0° C. was added Et3N (9 mL, 64.3 mMol) followed by 2-chlorocarbonyl-propionic acid ethyl ester (10 g, 60.8 mMol) dropwise over 15 minutes. The reaction was allowed to warm to RT and stirred for 4 h, poured into a separatory funnel, washed with water, brine, dried (Na2SO4), and evaporated to dryness under vacuum. The unpurified acylamidine (˜90% pure by LCMS, MS (ES) m/e (M+H)+434.4) was taken up in DMF (150 mL) and heated to 100° C. with stirring for 18 h. The reaction was concentrated under vacuum and purified by flash chromatography (90:10:1, CH2Cl2:EtOAc:HOAc) then (30:70:1, EtOAc:hexane:HOAc) to give the title compound (8.42 g, 41%) as an off-white solid: MS (ES) m/e 388.2 (M+H)+.

1. additionpoured into a separatory funnel
2. washwashed with water, brine
3. dry with materialdried (Na2SO4)
4. customevaporated to dryness under vacuum
5. temperatureheated to 100° C.
6. stirringwith stirring for 18 h
7. concentrationThe reaction was concentrated under vacuum
8. custompurified by flash chromatography (90:10:1, CH2Cl2:EtOAc:HOAc)