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

HRID 1794153ノート

反応式

HRID 1794153 の反応式
[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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-2526b19ad8104a7b9a42ba46e9a693c7
出典データセット
uspto-grants-2006_04
特許番号
US07022707B2

反応ノート

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