반응 #58613

반응 방정식

Me3Al

(S)-3-Amino-piperidine-1-carboxylic acid tert-butyl ester

Rochelle's salt

methyl 5-(4-methoxyphenyl)-2-({[(trichloroacetyl)amino]carbonyl}amino)thiophene-3-carboxylate

→

light yellow solid

수율 67.0%

tert-Butyl(3S)-3-({[2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-3-thienyl]carbonyl}amino)piperidine-1-carboxylate

수율 67.0%

용매

THF

EtOAc

H2O

THF

THF

반응 조건

후처리

1. 1
   온도The reaction mixture was cooled with ice
2. 2
   기타to quench
3. 3
   기타the reaction
4. 4
   온도The resulting biphasic solution was warmed to room temperature
5. 5
   workup.STIRRINGstirred for an additional 1 h
6. 6
   추출the aqueous layer was extracted with EtOAc (3×)
7. 7
   세척the combined organic extracts were washed with H2O, brine
8. 8
   건조dried (Na2SO4)
9. 9
   기타Evaporation
10. 10
    기타gave a pale orange solid
11. 11
    기타Purification by column chromatography (SiO2, 50% EtOAc/hexanes)

실험 절차

To a solution of methyl 5-(4-methoxyphenyl)-2-({[(trichloroacetyl)amino]carbonyl}amino)thiophene-3-carboxylate (1.0 g, 2.2 mmol) in dry THF (20 mL) was added a solution of [Me2Al-3-Boc-(S)-3-aminopiperidine] in THF (which was preformed by the addition of Me3Al (2.0 M in hexanes, 2.2 nL, 4.4 mmol) to a solution of (S)-3-Amino-piperidine-1-carboxylic acid tert-butyl ester (0.89 g, 4.4 mmol) in 10 mL THF at −78° C. followed by warming to room temperature for an additional 15 min). The resulting orange-colored solution was stirred overnight at room temperature. The reaction mixture was cooled with ice and a 10% aqueous solution of Rochelle's salt was added slowly to quench the reaction. The resulting biphasic solution was warmed to room temperature and stirred for an additional 1 h. The mixture was diluted with EtOAc and H2O, the aqueous layer was extracted with EtOAc (3×) and the combined organic extracts were washed with H2O, brine and dried (Na2SO4). Evaporation gave a pale orange solid. Purification by column chromatography (SiO2, 50% EtOAc/hexanes) gave 0.70 g (67%) of a light yellow solid. LC/MS (APCI, ES, M+H=475).

출처