Methyl iodide → HCID 66955034, compound
Reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[NH:8][C:9](=[O:17])[N:10]([CH2:12][O:13][CH2:14][CH2:15][CH3:16])[CH:11]=1)=[O:5])[CH3:2].[CH3:25][Si](C)(C)N[Si](C)(C)C.[K].CI.[NH4+].[Cl-]>C1COCC1>[CH2:1]([O:3][C:4]([C:6]1[CH:7]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[N:8]([CH3:25])[C:9](=[O:17])[N:10]([CH2:12][O:13][CH2:14][CH2:15][CH3:16])[CH:11]=1)=[O:5])[CH3:2]Participants
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 4-(4-Fluoro-phenyl)-2-oxo-1-propoxymethyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (152 mg, 0.39 mmol) in THF (3 mL) was added potassium hexamethyldisilazane (0.92 mL of 1M toluene solution, 0.46 mmol) at 0° C. under Ar. The mixture was stirred for 1 h at 0° C. Methyl iodide (0.23 mL of 2M solution in tert-butyl methyl ether) was added at 0° C., and the mixture was stirred at 0° C. overnight. Saturated aqueous NH4Cl was added, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with brine, dried under Na2SO4, filtered and concentrated to dryness under reduced pressure. Purification of the residue by flash column (hexane/ethyl acetate gradient) gave 4-(4-fluoro-phenyl)-3-methyl-2-oxo-1-propoxymethyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid ethyl ester (143 mg, 91%).
Workup
- stirringthe mixture was stirred at 0° C. overnight
- extractionthe mixture was extracted with ethyl acetate
- washThe combined organic layers were washed with brine
- customdried under Na2SO4
- filtrationfiltered
- concentrationconcentrated to dryness under reduced pressure
- customPurification of the residue by flash column (hexane/ethyl acetate gradient)
Sources & evidence
- ORD record
- ord-285b06498e4840d58c2ef7fb43b682af
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08435990B2
Reaction notes
Loading…