Sodium Hydroxide → 4-Methoxy-2-(methylsulfanyl)pyrimidine-5-carboxylic acid

HRID 1160434Notes

Reaction equation

HRID 1160434 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10]CC)=[O:9])=[CH:6][N:5]=[C:4]([S:13][CH3:14])[N:3]=1.[CH3:15][O-:16].[Na+].[OH-].[Na+]>CO.O>[CH3:15][O:16][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[CH:6][N:5]=[C:4]([S:13][CH3:14])[N:3]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 800084-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl esterHCID 10942334Sodium Methoxide

Product 1

HCID 128290034-Methoxy-2-(methylsulfanyl)pyrimidine-5-carboxylic acidYield 92%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of ethyl 4-chloro-2-(methylthio)pyrimidine-5-carboxylate (24.40 g, 104.9 mmol) in MeOH (125 mL) was added solid sodium methoxide (11.40 g, 211.0 mmol) at rt. The reaction mixture was stirred at rt for 5 h and then treated with NaOH (17.70 g, 315.5 mmol) in H2O (100 mL). It was then stirred at the same temperature for an additional 1 h. The reaction mixture was concentrated to half of the volume and then acidified to pH=4 with HCl (6N). The reaction was extracted with EtOAc (5×200 mL) and the organic layer was washed with brine (200 mL), dried over Na2SO4, and concentrated to yield the desired product as a white solid (19.28 g, 92%). MS (m/z): 201 (MH+). 1H NMR (DMSO-d6) δ: 8.72 (s, 1H), 3.98 (s, 3H), 2.54 (s, 3H).

Workup

  1. stirringIt was then stirred at the same temperature for an additional 1 h
  2. concentrationThe reaction mixture was concentrated to half of the volume
  3. extractionThe reaction was extracted with EtOAc (5×200 mL)
  4. washthe organic layer was washed with brine (200 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-e26475a66c1e425c9db977718dd5646e
Source dataset
uspto-grants-2010_10
Patent number
US07816406B2

Reaction notes

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