Methyl iodide → HCID 18326588, compound

HRID 1250702Notes

Reaction equation

HRID 1250702 reaction equation
C[O:2][C:3]([C:5]1[CH:6]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)[NH:7][C:8](=[O:12])[N:9]([CH3:11])[CH:10]=1)=[O:4].[H-].[Na+].[CH3:23]I.[OH-].[Na+]>CN(C=O)C.CO.CCCCCC.CCOC(C)=O.C1COCC1>[F:20][C:15]1[CH:14]=[C:13]([CH:6]2[C:5]([C:3]([OH:2])=[O:4])=[CH:10][N:9]([CH3:11])[C:8](=[O:12])[N:7]2[CH3:23])[CH:18]=[CH:17][C:16]=1[F:19]

Participants

10

Reactant 4

HCID 6328Methyl iodideHCID 14798Sodium Hydroxide2×HCID 24758Sodium hydrideHCID 20718795HCID 20718795, compound

Product 1

HCID 18326588HCID 18326588, compound

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 0.36 g (1.3 mmol) (−)-4-(3,4-Difluorophenyl)-1-methyl-2-oxo-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid methyl ester (the product of Example 10, Step C) in 3 ml DMF was added 0.068 g (2.8 mmol) sodium hydride. After the gas evolution had ceased (5 min), 0.10 ml (1.6 mmol) methyl iodide was added and the reaction mixture was stirred 2 hours at room temperature then poured into 100 ml EtOAc and washed 100 ml 5% aqueous KHSO4 solution, 100 ml water, and 100 ml brine; then dried over Na2SO4, filtered and concentrated in vacuo. The residue was dissolved in 5 ml MeOH and to this was added 0.2 ml (0.5 mmol, 2.5M solution in water) NaOH, 2 ml THF, and 0.8 ml (2 mmol, 2.5M solution in water) NaOH. The initially heterogeneous reaction mixture slowly became homogeneous, and after 6 hours, the reaction was poured into 75 ml EtOAc and extracted 2×75 ml H2O. The aqueous layer was acidified to pH=1 with concentrated HCl solution, solid NaCl was added and the mixture extracted 3×50 ml ethyl acetate. The combined ethyl acetate extracts were dried over Na2SO4, filtered and concentrated in vacuo. Toluene (50 ml) was added and removed in vacuo two times, and the residue was dissolved in 1 ml CH2Cl2 and 0.33 g of essentially pure solid was obtained by adding hexane. α25=−150° C.=0.37 MeOH. 1H NMR (300 MHz, CD3OD) d 7.45 (s, 1H); 7.28-7.12 (m, 3H); 5.25 (s, 1H); 3.21 (s, 3H); 2.82 (s, 3H).

Workup

  1. additionwas added
  2. washwashed 100 ml 5% aqueous KHSO4 solution, 100 ml water, and 100 ml brine
  3. dry with materialthen dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in 5 ml MeOH
  7. waitThe initially heterogeneous reaction mixture slowly became homogeneous, and after 6 hours
  8. extractionextracted 2×75 ml H2O
  9. additionwas added
  10. extractionthe mixture extracted 3×50 ml ethyl acetate
  11. dry with materialThe combined ethyl acetate extracts were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. additionToluene (50 ml) was added
  15. customremoved in vacuo two times
  16. dissolutionthe residue was dissolved in 1 ml CH2Cl2
  17. custom0.33 g of essentially pure solid was obtained

Sources & evidence

ORD record
ord-397aa4d2d06042199e27feaf8131fdba
Source dataset
uspto-grants-2002_01
Patent number
US06339090B1

Reaction notes

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