反应详情

(S)-2-Amino-3 -(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochloride (1.68 g, 4.65 mmol, Example 7, Step A) and BOC-Leu-CHO ((tert-butoxy)-N-[1-(2-methylpropyl)-2-oxoethyl]carboxamide) (1.00 g, 4.65 mmol, Peninsula Laboratories, Belmont, Calif.) were mixed in CH2Cl2 (25 mL). After stirring at ambient temperature under nitrogen atmosphere for 30 minutes, the solution was cooled to 0° C. in an ice-water bath. To this solution was added sodium triacetoxyborohydride (1.50 g, 6.98 mmol). The resulting reaction mixture was stirred for, in succession, 30 minutes at 0° C. and 12 hours at ambient temperature. Twenty-five milliliters of saturated aqueous NaHCO3 solution was added to the reaction mixture, and the resulting mixture was stirred for 5 minutes. The 2 layers were separated, and the aqueous layer was extracted with CH2Cl2 (2×30 mL). The combined organic solution was dried over Na2SO4. The solution was concentrated in vacuo affording a viscous oil. The reaction gave two diastereomers which were purified twice by column chromatography (eluant used in first column chromatography: 30% EtOAc-4% MeOH-66% hexanes; eluant used in second column chromatography: 100% acetonitrile). When the solvent system, 30% EtOAC-66% benzene-4% MeOH, was used as eluant, The two diastereomers gave different Rf values on TLC (0.68 and 0.53). The compound with a Rf value of 0.53 was isolated by preparative plate as a yellow oil (0.27 g) and used in used step.

1. temperaturethe solution was cooled to 0° C. in an ice-water bath
2. customThe resulting reaction mixture
3. stirringwas stirred for, in succession, 30 minutes at 0° C.
4. custom12 hours
5. customat ambient temperature
6. stirringthe resulting mixture was stirred for 5 minutes
7. customThe 2 layers were separated
8. extractionthe aqueous layer was extracted with CH2Cl2 (2×30 mL)
9. dry with materialThe combined organic solution was dried over Na2SO4
10. concentrationThe solution was concentrated in vacuo
11. customaffording a viscous oil
12. customThe reaction gave two diastereomers which
13. customwere purified twice by column chromatography (eluant used in first column chromatography: 30% EtOAc-4% MeOH-66% hexanes; eluant used in second column chromatography: 100% acetonitrile)
14. customThe two diastereomers gave different Rf values on TLC (0.68 and 0.53)