Hydrochloric Acid → (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid 1-cyclohexyloxycarbonyloxy-ethyl ester

HRID 448644노트

반응식

HRID 448644 반응식
[C:1](=[O:13])([O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)[O:2][CH:3](Cl)[CH3:4].[C:14]1([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:19]=[CH:18][C:17]([CH2:20][C@@H:21]([NH:30]C(OC(C)(C)C)=O)[CH2:22][C@:23]([CH2:28][OH:29])([CH3:27])[C:24]([OH:26])=[O:25])=[CH:16][CH:15]=1.CCN(CC)CC.Cl.O1CCOCC1>CC(C)=O.CC#N>[CH:7]1([O:6][C:1]([O:2][CH:3]([O:26][C:24](=[O:25])[C@@:23]([CH2:28][OH:29])([CH3:27])[CH2:22][C@H:21]([NH2:30])[CH2:20][C:17]2[CH:18]=[CH:19][C:14]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[CH:15][CH:16]=2)[CH3:4])=[O:13])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1

참가 물질

8

반응물 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 112295291-Chloroethyl Cyclohexyl CarbonateHCID 68181022(2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid

생성물 1

HCID 68181297(2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid 1-cyclohexyloxycarbonyloxy-ethyl ester

시약·촉매·용매 2

HCID 180Acetone용매HCID 6342Acetonitrile용매

실험 절차

1-Chloroethyl cyclohexyl carbonate (240 mg, 1.2 mmol) was added to a mixture of (2S,4R)-5-biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid (300 mg, 726 μmol) and Et3N (106 μL, 762 μmol) in acetone (10 mL). The mixture was refluxed for 24 hours and the reaction monitored for completion. The individual isomers were separated (˜1:1) and purified (Interchim reverse phase chromatography column) the solvent was removed under vacuum. MeCN (2 mL) and 4 M HCl in 1,4-dioxane (3 mL, 10 mmol) was added and the resulting mixture was stirred for 30 minutes. The solvent was evaporated under vacuum and the product was azeotroped with toluene (1×) to yield (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid 1-cyclohexyloxycarbonyloxy-ethyl ester.

후처리

  1. temperatureThe mixture was refluxed for 24 hours
  2. customThe individual isomers were separated (˜1:1)
  3. custompurified (Interchim reverse phase chromatography column) the solvent
  4. customwas removed under vacuum
  5. customThe solvent was evaporated under vacuum
  6. customthe product was azeotroped with toluene (1×)

출처 및 근거

ORD 기록
ord-408832e6487f40b8ad3a0e4872f6cecf
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481044B2

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