Hydrochloric Acid → HCID 178500062, compound
Reaction equation
C[O-].[Na+].CO.C[O:7][C:8](=O)[CH2:9][C:10]([O:12]C)=O.[F:15][C:16]([F:25])([F:24])/[CH:17]=[CH:18]/[C:19]([O:21][CH2:22]C)=[O:20].C(O)(=O)C.[CH:30]([NH2:32])=[NH:31].Cl>>[OH:7][C:8]1[C:9]([CH:17]([C:16]([F:25])([F:24])[F:15])[CH2:18][C:19]([O:21][CH3:22])=[O:20])=[C:10]([OH:12])[N:32]=[CH:30][N:31]=1Participants
Conditions
- Temperature
- 62 °C
Procedure
Heat a solution of 25% sodium methoxide in methanol (1.49 L, 0.86 eq) at 62° C. Add a mixture of propanedioic acid dimethyl ester (1.00 kg, 7.57 mol) and ethyl 4,4,4-trifluorocrotonate (1.27 kg, 1.0 eq) dropwise over two hours. Heat the mixture at 62° C. for two hours. Cool the mixture to 30° C. Add 25% sodium methoxide in methanol (2.34 L, 1.35 eq) and formamidine acetate (867.2 g, 1.1 eq). Stir at 30° C. overnight. Cool the mixture to 0° C. and add 5 M aqueous hydrochloric acid, adjusting the pH to 4.5. Filter and wash with water (2 L). To the wet solid, add methyl tert-butyl ether (5 L). Filter, wash with additional methyl tert-butyl ether (2 L), and dry at 50° C. to give methyl 3-(4,6-dihydroxypyrimidin-5-yl)-4,4,4-trifluorobutanoate (1.05 kg, 52%).
Workup
- additionAdd
- temperatureCool the mixture to 30° C
- temperatureCool the mixture to 0° C.
- filtrationFilter
- washwash with water (2 L)
- additionTo the wet solid, add methyl tert-butyl ether (5 L)
- filtrationFilter
- washwash with additional methyl tert-butyl ether (2 L)
- customdry at 50° C.
Sources & evidence
- ORD record
- ord-c9c480315f67411fa0b4990f8dfbb00c
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08436002B2
Reaction notes
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