Phosphorus oxychloride → Ethyl 4-(2-bromo-4-fluorophenyl)-2-chloro-6-methyl-1,4-dihydropyrimidine-5-carboxylate

HRID 524698Notes

Reaction equation

HRID 524698 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:13]([CH3:20])[NH:12][C:11](=O)[NH:10]1.O=P(Cl)(Cl)[Cl:24]>>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:13]([CH3:20])[NH:12][C:11]([Cl:24])=[N:10]1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 90043988Ethyl 4-(2-bromo-4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate

Product 1

HCID 118107507Ethyl 4-(2-bromo-4-fluorophenyl)-2-chloro-6-methyl-1,4-dihydropyrimidine-5-carboxylateYield 46%

Conditions

Temperature
110 °C

Procedure

A mixture of ethyl 4-(2-bromo-4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (3.56 g, 10 mmol) and POCl3 (15 mL) was stirred at 110° C. for 4 hours under N2, then cooled to 25° C. POCl3 was removed in vacuo and the residue was dissolved in chloroform (100 mL). Then the mixture was adjusted to pH 6-8 with strong ammonia. The organic phase was washed with brine (80 mL×3), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo. The residue was purified by a silica gel column chromatography (PETROLEUM ETHER/EtOAc (V/V)=5/1) to give the title compound as a white solid (1.73 g, 46%). The compound was characterized by the following spectroscopic data:

Workup

  1. temperaturecooled to 25° C
  2. customPOCl3 was removed in vacuo
  3. dissolutionthe residue was dissolved in chloroform (100 mL)
  4. washThe organic phase was washed with brine (80 mL×3)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customThe residue was purified by a silica gel column chromatography (PETROLEUM ETHER/EtOAc (V/V)=5/1)

Sources & evidence

ORD record
ord-fbb5430510e34314b6a9466aa1856f8b
Source dataset
uspto-grants-2016_05
Patent number
US09340538B2

Reaction notes

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