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

HRID 1794153Notes

Reaction equation

HRID 1794153 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-2526b19ad8104a7b9a42ba46e9a693c7
Source dataset
uspto-grants-2006_04
Patent number
US07022707B2

Reaction notes

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