Hydrochloric Acid → (R)-2-Ethyl-piperazine-1-carboxylic acid 2,6-difluoro-3-methoxy-benzyl ester hydrochloride

HRID 1794153노트

반응식

HRID 1794153 반응식
[H-].[Na+].[F:3][C:4]1[C:28]([OH:29])=[CH:27][CH:26]=[C:25]([F:30])[C:5]=1[CH2:6][O:7][C:8]([N:10]1[CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][C@H:11]1[CH2:23][CH3:24])=[O:9].[CH3:31]I.[ClH:33]>CN(C=O)C>[ClH:33].[F:3][C:4]1[C:28]([O:29][CH3:31])=[CH:27][CH:26]=[C:25]([F:30])[C:5]=1[CH2:6][O:7][C:8]([N:10]1[CH2:15][CH2:14][NH:13][CH2:12][C@H:11]1[CH2:23][CH3:24])=[O:9]

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 69142665(R)-2-Ethyl-piperazine-1,4-dicarboxylic acid 4-tert-butyl ester 1-(2,6-difluoro-3-hydroxy-benzyl)ester

생성물 1

HCID 69144072(R)-2-Ethyl-piperazine-1-carboxylic acid 2,6-difluoro-3-methoxy-benzyl ester hydrochloride수율 75%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A mixture of 5.03 mg (0.126 mmol) NaH (60% suspension in mineral oil) and 33.6 mg (0.084 mmol) (R)-2-Ethyl-piperazine-1,4-dicarboxylic acid 4-tert-butyl ester 1-(2,6-difluoro-3-hydroxy-benzyl) ester in 1 ml DMF was stirred for 30 min at room temperature under argon. 13.1 mg (0.092 mmol) methyliodide was added and the mixture was stirred 30 min at room temperature. After addition of 0.06 ml HCl (37%) the mixture was purified with preparative HPLC eluting with an acetonitrile/water gradient. The fractions containing the desired intermediate were combined and evaporated to dryness. The residue was taken up in 1 ml dioxane and 0.125 ml HCl (37%) and stirred for 30 min at 60° C. Evaporation of the mixture yielded 22 mg (75%) of the title compound. MS (ISP): 315 (M+H)+.

후처리

  1. stirringthe mixture was stirred 30 min at room temperature
  2. customwas purified with preparative HPLC
  3. washeluting with an acetonitrile/water gradient
  4. additionThe fractions containing the desired intermediate
  5. customevaporated to dryness
  6. stirring0.125 ml HCl (37%) and stirred for 30 min at 60° C
  7. customEvaporation of the mixture

출처 및 근거

ORD 기록
ord-2526b19ad8104a7b9a42ba46e9a693c7
출처 데이터셋
uspto-grants-2006_04
특허 번호
US07022707B2

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