Hydrochloric Acid → (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid (S)-2-methoxycarbonylamino-3-methyl-butyryloxymethyl ester

HRID 523426노트

반응식

HRID 523426 반응식
Cl[CH2:2][O:3][C:4](=[O:14])[C@@H:5]([NH:9][C:10]([O:12][CH3:13])=[O:11])[CH:6]([CH3:8])[CH3:7].[C:15]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:20]=[CH:19][C:18]([CH2:21][C@@H:22]([NH:31]C(OC(C)(C)C)=O)[CH2:23][C@:24]([CH2:29][OH:30])([CH3:28])[C:25]([OH:27])=[O:26])=[CH:17][CH:16]=1.CCN(CC)CC.Cl.O1CCOCC1>CC(C)=O.CC#N>[CH3:13][O:12][C:10]([NH:9][C@@H:5]([CH:6]([CH3:8])[CH3:7])[C:4]([O:3][CH2:2][O:27][C:25](=[O:26])[C@@:24]([CH2:29][OH:30])([CH3:28])[CH2:23][C@H:22]([NH2:31])[CH2:21][C:18]1[CH:19]=[CH:20][C:15]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)=[CH:16][CH:17]=1)=[O:14])=[O:11]

참가 물질

8

반응물 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 68181022(2S,4R)-5-Biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acidHCID 86669865(S)-chloromethyl 2-((methoxycarbonyl)amino)-3-methylbutanoate

생성물 1

HCID 86669864(2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid (S)-2-methoxycarbonylamino-3-methyl-butyryloxymethyl ester

시약·촉매·용매 2

HCID 180Acetone용매HCID 6342Acetonitrile용매

실험 절차

(S)-2-Methoxycarbonylamino-3-methyl-butyric acid chloromethyl ester (140 mg, 630 μmol) was added to a mixture of (2S,4R)-5-biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid (0.2 g, 484 μmol) and Et3N (71 μL, 508 μmol) in acetone (10 mL). The mixture was refluxed for 24 hours and the reaction monitored for completion. When the reaction was complete, the product was purified (Interchim reverse phase chromatography column) the solvent was removed under vacuum. MeCN (2 mL) and 4 M HCl in 1,4-dioxane (2 mL, 8 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 (S)-2-methoxycarbonylamino-3-methyl-butyryloxymethyl ester.

후처리

  1. temperatureThe mixture was refluxed for 24 hours
  2. customthe product was purified (Interchim reverse phase chromatography column) the solvent
  3. customwas removed under vacuum
  4. customThe solvent was evaporated under vacuum
  5. customthe product was azeotroped with toluene (1×)

출처 및 근거

ORD 기록
ord-836c54cd67834e00bf8e3fcb69b3a5b9
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09334245B2

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