Dimethoxymethane → 3-methoxymethyl-2-phenyl-6-trifluoromethyl-4(3H)-pyrimidinone

HRID 1455

Reaction equation

HRID 1455 reaction equation
[C:1]1([C:7]2[NH:12][C:11](=[O:13])[CH:10]=[C:9]([C:14]([F:17])([F:16])[F:15])[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:18][O:19][CH2:20]OC.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[OH-].[Na+]>CCCCCC.C(Cl)Cl.C(OCC)(=O)C.C(Cl)(Cl)Cl>[CH3:18][O:19][CH2:20][N:12]1[C:11](=[O:13])[CH:10]=[C:9]([C:14]([F:16])([F:17])[F:15])[N:8]=[C:7]1[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

9

Reactant 4

HCID 8020DimethoxymethaneHCID 14798Sodium HydroxideHCID 14812Phosphorus oxide (P4O10)2×HCID 1354100074-Hydroxy-2-phenyl-6-(trifluoromethyl)pyrimidine

Product 1

HCID 196906963-methoxymethyl-2-phenyl-6-trifluoromethyl-4(3H)-pyrimidinoneYield 32.8%

Reagents, catalysts & solvents 4

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1.5 g (5.9 mmol) of 2-phenyl-6-trifluoromethyl-4(3H)-pyrimidinone, 17.2 g (226.3 mmol) dimethoxymethane, and 35 mL of chloroform was added 2.5 g (17.6 mmol) phosphorous pentoxide, at room temperature. By TLC (25% ethyl acetate in hexane) the reaction was incomplete after 4 h and an additional 3 g (21.1 mmol) phosphorous pentoxide was added. Stirring was continued for 16 h. The reaction mixture was poured onto crushed ice and 1M sodium hydroxide and methylene chloride were added. The layers were separated and the aqueous layer was extracted twice with methylene chloride. The organic extracts were combined and washed with brine, then dried over MgSO4 and concentrated to yield 1.1 g crude product, which was purified by recrystallization from hexane. Thus, 0.55 g (32%) 3-methoxymethyl-2-phenyl-6-trifluoromethyl-4(3H)-pyrimidinone (Compound 6) as a yellow solid was obtained. 1H-NMR (CDCl3) δ 3.55(3H,s); 5.2(2H,d); 6.85(1H,s); 7.65(3H,m); 7.75(2H,m).

Workup

  1. customat room temperature
  2. additionThe reaction mixture was poured
  3. additionwere added
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted twice with methylene chloride
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customto yield 1.1 g crude product, which
  10. customwas purified by recrystallization from hexane

Sources & evidence

ORD record
ord-8a76bfee244c4e589316dfef7559347f
Source dataset
uspto-grants-1998_03
Patent number
US05726124

Linked notes

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