Ethanol → (2R,4S)-4-amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochloride

HRID 1021034노트

반응식

HRID 1021034 반응식
[C:1]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@@H:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:9][C@@H:10]([CH3:14])[C:11]([OH:13])=[O:12])=[CH:3][CH:2]=1.S(Cl)([Cl:31])=O.[CH2:33](O)[CH3:34]>>[ClH:31].[CH2:33]([O:13][C:11](=[O:12])[C@H:10]([CH3:14])[CH2:9][C@H:8]([NH2:15])[CH2:7][C:4]1[CH:5]=[CH:6][C:1]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[CH:2][CH:3]=1)[CH3:34].[C:1]1([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@@H:8]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH2:9][C@@H:10]([CH3:14])[C:11]([OH:13])=[O:12])=[CH:5][CH:6]=1

참가 물질

5

반응물 3

HCID 702EthanolHCID 24386Thionyl ChlorideHCID 46193546(2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acid

생성물 2

HCID 25017086(2R,4S)-4-amino-5-(biphenyl-4-yl)-2-methylpentanoic acid ethyl ester hydrochlorideHCID 46193546(2R,4S)-2-methyl-4-((2-methylpropan-2-yl)oxycarbonylamino)-5-(4-phenylphenyl)pentanoic acid

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온도
65 °C

실험 절차

150 g (2R,4S)-5-biphenyl-4-yl-4-tert-butoxycarbonylamino-2-methylpentanoic acid (3-a, R1=BOC, R2=R3=H) are added to 1500 ml ethanol at room temperature. The mixture is then warmed to an internal temperature of 60-70° C. 42.8 ml Thionyl chloride is then added over a period of 1 h to the reaction mixture. The mixture is then stirred for a further 2 h. 810 ml of the solvent is removed by distillation under reduced pressure. 1460 ml Heptane fraction is then added. 1310 ml of solvent is then removed by distillation under reduced pressure. 1460 ml Heptane fraction is then added. 520 ml of solvent is then removed by distillation under reduced pressure. 1460 ml Heptane fraction is then added. The mixture is then cooled to room temperature over a period of 1 h. The mixture is then stirred at room temperature for 2 h. The solid is then collected by filtration. The solid is then washed with heptane fraction (600 ml) and dried to give (2R,4S)-4-amino-5-biphenyl-4-yl-2-methylpentanoic acid ethyl ester hydrochloride (3-a, R1=R2=H, R3=Et). Spectroscopic data as given in Example 9-1 Method 1.

후처리

  1. custom810 ml of the solvent is removed by distillation under reduced pressure
  2. addition1460 ml Heptane fraction is then added
  3. custom1310 ml of solvent is then removed by distillation under reduced pressure
  4. addition1460 ml Heptane fraction is then added
  5. custom520 ml of solvent is then removed by distillation under reduced pressure
  6. addition1460 ml Heptane fraction is then added
  7. temperatureThe mixture is then cooled to room temperature over a period of 1 h
  8. stirringThe mixture is then stirred at room temperature for 2 h
  9. filtrationThe solid is then collected by filtration
  10. washThe solid is then washed with heptane fraction (600 ml)
  11. customdried

출처 및 근거

ORD 기록
ord-6d9fa91278254b4b8e26cafd169c3de3
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08716495B2

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