4-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl ester → HCID 178503463, compound

HRID 348490Notes

Reaction equation

HRID 348490 reaction equation
C[Si]([O:5][Si](C)(C)C)(C)C.[K].C([O:13][C:14]([C:16]1[C:17](Cl)=[N:18][C:19]([S:22][CH3:23])=[N:20][CH:21]=1)=[O:15])C>COCCOC>[OH:5][C:17]1[C:16]([C:14]([OH:13])=[O:15])=[CH:21][N:20]=[C:19]([S:22][CH3:23])[N:18]=1

Participants

4

Reactant 2

HCID 800084-Chloro-2-(methylthio)pyrimidine-5-carboxylic acid ethyl esterHCID 86599933Potassium trimethylsilyloxide

Product 1

HCID 178503463HCID 178503463, compoundYield 73.4%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

A slurry of potassium trimethylsilyl oxide (90% tech., 40 g, 0.31 mol) in 1,2-dimethoxyethane (300 mL) was added, slowly over 20 min, to a solution of ethyl-4-chloro-2-methylthio-5-pyrimidinecarboxylate (Aldrich, 15 g, 64 mmol) in 1,2-dimethoxyethane (100 mL). Said addition, being mildly exothermic, may warrant the use of an ice bath to maintain ambient temperature conditions during addition. After addition was complete, the resulting suspension was stirred at ambient temperature for 1 h, then warmed to reflux for 36 h, then allowed to cool to ambient temperature. Reaction mixture was quenched with 1 M HCl(aq), then extracted with ethyl acetate and dried using sodium sulfate to produce a crude solid (11 g). Said crude solid was then recrystallized in ethyl acetate to afford 4-hydroxy-2-methylsulfanylpyrimidine-5-carboxylic acid as a white solid (8.8 g, 47 mmol, 73% yield). MS (−ESI) m/z 185 (M−, 100). An aliquot of this material (3.00 g, 16.1 mmol) was diluted with thionyl chloride (90 mL) followed by DMF (0.20 mL) and the resulting solution was warmed to reflux. After 1 hour at reflux, the solution was allowed to cool to ambient temperature and was concentrated in vacuo to afford a beige solid which was triturated once from hot toluene and then once again from hot hexanes (i.e., in both instances the soluble material was the desired fraction). This afforded, after concentration in vacuo, the titled compound as a white solid (3.90 g, 15.6 mmol, 97% yield). 1H NMR (300 MHz, CDCl3) δ 9.15 (s, 1H), 2.63 (s, 3H).

Workup

  1. additionaddition
  2. additionduring addition
  3. additionAfter addition
  4. temperaturewarmed
  5. temperatureto reflux for 36 h
  6. temperatureto cool to ambient temperature
  7. customReaction mixture
  8. customwas quenched with 1 M HCl(aq)
  9. extractionextracted with ethyl acetate
  10. customdried
  11. customto produce a crude solid (11 g)
  12. customwas then recrystallized in ethyl acetate

Sources & evidence

ORD record
ord-e29f3a9033224a5ca9ae8ffa3111d5e9
Source dataset
uspto-grants-2007_02
Patent number
US07176310B1

Reaction notes

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