Toluene → N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine Methyl Ester

HRID 55737

반응식

HRID 55737 반응식
[CH:1]([C:4]1[S:5][CH:6]=[C:7]([CH2:9][NH:10][CH3:11])[N:8]=1)([CH3:3])[CH3:2].O([C:19]([NH:21][C@H:22]([C:26]([OH:28])=[O:27])[CH:23]([CH3:25])[CH3:24])=[O:20])C1C=CC=CC=1.[C:29]1(C)C=CC=CC=1.CCCCCCC>CCOC(C)=O>[CH3:29][O:28][C:26](=[O:27])[C@H:22]([CH:23]([CH3:24])[CH3:25])[NH:21][C:19]([N:10]([CH3:11])[CH2:9][C:7]1[N:8]=[C:4]([CH:1]([CH3:3])[CH3:2])[S:5][CH:6]=1)=[O:20]

참가 물질

6

반응물 4

HCID 1140TolueneHCID 8900HeptaneHCID 9816135N-Phenoxycarbonyl-L-valineHCID 107496872-Isopropyl-4-(N-methyl)amino-methyl thiazole

생성물 1

HCID 10520283N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine Methyl Ester수율 76.9%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

반응 조건

온도
110 °C

실험 절차

Into a 500 ml 3-neck round bottom flask equipped with mechanical stirrer, nitrogen atmosphere, thermocouple, heating mantle and condensor was charged the product of Example 73B (28.1 g, 0.165 mols), phenoxycarbonyl-(L)-valine (41.5 g, 0.165 mol) and 155 ml toluene. This solution was warmed to reflux (110° C.) and stirred for three hours, then cooled to 20°±5° C. and washed with 2×69 ml 10% citric acid followed by 1×69 ml water, 1×116 mls 4% sodium hydroxide, 1×58 ml 4% sodium hydroxide and finally 1×58 ml water. The organic product solution was then treated with 3 grams of activated carbon at reflux for 15 minutes, filtered through infusorial earth to remove carbon, and the carbon/infusorial earth cake was washed with 25 ml hot toluene. Next the solvent was removed to afford a brown oil which solidified upon cooling. This brown solid was dissolved with warming in 31 ml EtOAc and 257 ml heptane at 60°±5° C. This solution was slowly cooled to 25° C., stirred 12 hours, cooled further to 0° C., and stirred 3 hours. The crystals were collected by filtration and washed with 50 ml 1:9 EtOAc/Heptane. The solid was dried in a 50° C. vacuum oven for 12 hours to afford 41.5 grams of the desired product as a tan-colored solid (76.9%).

후처리

  1. customInto a 500 ml 3-neck round bottom flask equipped with mechanical stirrer
  2. temperaturenitrogen atmosphere, thermocouple, heating mantle
  3. temperatureThis solution was warmed
  4. temperaturecooled to 20°±5° C.
  5. washwashed with 2×69 ml 10% citric acid
  6. additionThe organic product solution was then treated with 3 grams of activated carbon
  7. temperatureat reflux for 15 minutes
  8. filtrationfiltered through infusorial earth
  9. customto remove carbon
  10. washthe carbon/infusorial earth cake was washed with 25 ml hot toluene
  11. customNext the solvent was removed
  12. customto afford a brown oil which
  13. temperatureupon cooling
  14. dissolutionThis brown solid was dissolved
  15. customat 60°±5° C
  16. temperatureThis solution was slowly cooled to 25° C.
  17. stirringstirred 12 hours
  18. temperaturecooled further to 0° C.
  19. stirringstirred 3 hours
  20. filtrationThe crystals were collected by filtration
  21. washwashed with 50 ml 1:9 EtOAc/Heptane
  22. customThe solid was dried in a 50° C. vacuum oven for 12 hours

출처 및 근거

ORD 기록
ord-da0e3f4e11a64937aa741f013073da17
출처 데이터셋
uspto-grants-1997_04
특허 번호
US05625072

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