Реакция #516315

Уравнение реакции

NaHCO3

(S)-2-Amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide monohydrochloride

BOC-Leu-CHO

sodium triacetoxyborohydride

→

oil

Выход 12.3%

(1-{[2-(4-Benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethylamino]-methyl}-3-methyl-butyl)-carbamic acid tert-butyl ester

Выход 12.3%

Растворители

CH2Cl2

Условия реакции

Обработка

1. 1
   Температураthe solution was cooled to 0° C. in an ice-water bath
2. 2
   ДругоеThe resulting reaction mixture
3. 3
   workup.STIRRINGwas stirred for, in succession, 30 minutes at 0° C.
4. 4
   Другое12 hours
5. 5
   Другоеat ambient temperature
6. 6
   workup.STIRRINGthe resulting mixture was stirred for 5 minutes
7. 7
   ДругоеThe two layers were separated
8. 8
   Экстракцияthe aqueous layer was extracted with CH2Cl2 (2×30 mL)
9. 9
   СушкаThe combined organic solution was dried over Na2SO4
10. 10
    КонцентрированиеThe solution was concentrated in vacuo
11. 11
    Другоеaffording a viscous oil
12. 12
    ДругоеThe reaction gave two diastereomers which
13. 13
    Другоеwere 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. 14
    ДругоеThe two diastereomers gave different Rf values on TLC (0.68 and 0.53)

Методика

(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 two 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 0.68 was isolated by preparative plate as a yellow oil (0.3 g) and used in used step.

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