Hydrochloric Acid → Ethyl 2-cyano-2-[4-methyl-6-(trifluoromethyl)pyrimidin-2-yl]acetate hydrochloride salt

HRID 1091681Notes

Reaction equation

HRID 1091681 reaction equation
[H-].[Na+].[C:3]([CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])#[N:4].[CH3:11][C:12]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:15]=[C:14](S(C)(=O)=O)[N:13]=1.[ClH:26]>C1COCC1.O>[ClH:26].[C:3]([CH:5]([C:14]1[N:13]=[C:12]([CH3:11])[CH:17]=[C:16]([C:18]([F:21])([F:19])[F:20])[N:15]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])#[N:4]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7764Ethyl cyanoacetateHCID 24758Sodium hydrideHCID 111491404-Methyl-2-(methylsulfonyl)-6-(trifluoromethyl)pyrimidine

Product 1

HCID 66593642Ethyl 2-cyano-2-[4-methyl-6-(trifluoromethyl)pyrimidin-2-yl]acetate hydrochloride salt

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1,1,1-trifluoro-2,4-pentanedione (5.00 g; 32.4 mmol) and S-methylisothiourea hemisulfate (4.06 g; 29.2 mmol) in pyridine (3.75 mL) and water (62 mL) was heated at reflux for 1 day. The mixture was cooled to room temperature, extracted with chloroform, and the chloroform extract washed with water to give 4-methyl-2-(methylthio)-6-(trifluoromethyl)pyrimidine as an off-white solid (4.60 g, 22.1 mmol). This was dissolved in MeOH (60 mL), and a solution of OXONE® (27.1 g, 44.2 mmol) in water (100 mL) was added over 10 min. The mixture was stirred at room temperature for 4 hr and then extracted with EA. The EA was washed with water, dried, and concentrated to give 4-methyl-2-(methylsulfonyl)-6-(trifluoromethyl)pyrimidine (4.8 g) as a white solid. Sodium hydride (0.16 g of a 60% dispersion in mineral oil; 4.0 mmol) was added to a stirred solution of ethyl cyanoacetate (0.21 mL; 2.0 mmol) in THF (8 mL), and the resulting suspension stirred at room temperature for 15 min. 4-Methyl-2-(methylsulfonyl)-6-(trifluoromethyl)pyrimidine (0.48 g; 2.0 mmol) was then added, and the mixture stirred overnight. Water was added, followed by 1M hydrochloric acid to adjust to pH 3-4. The solid that formed solid was filtered, washed with water, and dried under high vacuum to give ethyl 2-cyano-2-[4-methyl-6-(trifluoromethyl)pyrimidin-2-yl]acetate hydrochloride salt (0.43 g) as a pale yellow solid.

Workup

  1. stirringthe mixture stirred overnight
  2. customThe solid that formed solid
  3. filtrationwas filtered
  4. washwashed with water
  5. customdried under high vacuum

Sources & evidence

ORD record
ord-4b16b3f6886444479777eb1152c49c57
Source dataset
uspto-grants-2012_03
Patent number
US08129396B2

Reaction notes

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