Hydrochloric Acid → (R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic Acid Ethyl Ester

HRID 541497노트

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HRID 541497 반응식
[CH3:1][O:2][C:3](=[O:24])[C@H:4]([OH:23])[CH2:5][N:6]([CH2:15][C:16]1[CH:21]=[CH:20][C:19](Br)=[CH:18][CH:17]=1)[NH:7]C(OC(C)(C)C)=O.[Cl:25][C:26]1[CH:27]=[CH:28][C:29]([F:35])=[C:30](B(O)O)[CH:31]=1.[C:36]([O-])([O-])=O.[K+].[K+].O.Cl.O1CCOCC1>CCOCC.[Pd].CCO>[CH2:1]([O:2][C:3](=[O:24])[C@H:4]([OH:23])[CH2:5][N:6]([CH2:15][C:16]1[CH:17]=[CH:18][C:19]([C:28]2[CH:27]=[C:26]([Cl:25])[CH:31]=[CH:30][C:29]=2[F:35])=[CH:20][CH:21]=1)[NH2:7])[CH3:36]

참가 물질

10

반응물 6

HCID 313Hydrochloric AcidHCID 962WaterHCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 3718925(5-Chloro-2-fluoro-phenyl)boronic acidHCID 67972599(R)-3-[N-(4-Bromobenzyl)-N'-t-butoxycarbonylhydrazino]-2-hydroxypropionic acid methyl ester

생성물 1

HCID 67972425(R)-3-[N-(5'-Chloro-2'-fluorobiphenyl-4-ylmethyl)hydrazino]-2-hydroxypropionic Acid Ethyl Ester수율 15.3%

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 702Ethanol용매3회HCID 3283Diethyl Ether용매

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온도
90 °C

실험 절차

(R)-3-[N-(4-Bromobenzyl)-N′-t-butoxycarbonylhydrazino]-2-hydroxypropionic acid methyl ester (1.0 g, 2.5 mmol), 5-chloro-2-fluorophenylboronic acid (865 mg, 5.0 mmol), and K2CO3 (857 mg, 6.2 mmol), were combined in EtOH (30 mL, 500 mmol) and water (8 mL, 400 mmol), followed by the addition of SilicaCat® DPP-Pd (0.28 mmol/g loading; 886 mg, 248 μmol). The mixture was heated at 90° C. until the reaction was complete (2 hours). The precipitate was filtered off, and the filtrate was concentrated and purified by reverse phase chromatography (30-95% MeCN in water with 0.5% TFA). The clean fractions were collected, lyophilized, and combined with 4 M HCl in dioxane (8 mL, 30 mmol) and EtOH (10 mL, 200 mmol). The resulting mixture was stirred at room temperature until the reaction was complete (7 hours). The mixture was concentrated to yield an oil, which was stirred in ether with few drops of EtOH overnight. The precipitate was filtered off and rinsed with ether to yield the title compound (140 mg).

후처리

  1. custom(2 hours)
  2. filtrationThe precipitate was filtered off
  3. concentrationthe filtrate was concentrated
  4. custompurified by reverse phase chromatography (30-95% MeCN in water with 0.5% TFA)
  5. customThe clean fractions were collected
  6. custom(7 hours)
  7. concentrationThe mixture was concentrated
  8. customto yield an oil, which
  9. filtrationThe precipitate was filtered off
  10. washrinsed with ether

출처 및 근거

ORD 기록
ord-d76382975b4f400293c84b9b50efda38
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871792B2

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