Isopropanol → 6-Isopropoxy-5-piperidin-1-yl-pyrazine-2-carboxylic acid

HRID 639325

Reaction equation

HRID 639325 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[N:9][C:8]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[C:7](Br)[N:6]=1)=[O:4].[CH:18]([OH:21])([CH3:20])[CH3:19].[H-].[Na+].[OH-].[K+]>O1CCOCC1.CN(C=O)C.C(O)=O.O>[CH:18]([O:21][C:7]1[N:6]=[C:5]([C:3]([OH:2])=[O:4])[CH:10]=[N:9][C:8]=1[N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)([CH3:20])[CH3:19]

Participants

9

Reactant 4

HCID 3776IsopropanolHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 866195226-Bromo-5-piperidin-1-yl-pyrazine-2-carboxylic acid methyl ester

Product 1

HCID 685694516-Isopropoxy-5-piperidin-1-yl-pyrazine-2-carboxylic acidYield 21.3%

Reagents, catalysts & solvents 4

HCID 284Formic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 0.212 g (0.707 mmol) 6-bromo-5-piperidin-1-yl-pyrazine-2-carboxylic acid methyl ester, 0.006 g (0.778 mmol) isopropanol and 0.034 g (0.778 mmol) NaH (55% dispersion in oil) in 1.7 mL dioxane was heated to 60° C. for 16 h. Water and 5N KOH was added and the mixture was heated to 50° C. for 4 h. Formic acid and DMF was added and the mixture was subjected to purification by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and formic acid. The product fractions were combined and evaporated to yield 0.04 g (21%) of the title compound. m/z (ES+): 266.4 (M+H).

Workup

  1. temperaturethe mixture was heated to 50° C. for 4 h
  2. customthe mixture was subjected to purification by preparative HPLC on reversed phase
  3. washeluting with a gradient
  4. customformed from acetonitrile, water and formic acid
  5. customevaporated

Sources & evidence

ORD record
ord-3fb8e08a922a48e4bc637cbb983a6acc
Source dataset
uspto-grants-2010_04
Patent number
US07691863B2

Linked notes

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