Chlorodifluoromethane → Benzoic acid, 2-chloro-5-(3-(difluoromethyl)-3,6-dihydro-4-methyl-2,6-dioxo-1(2H)-pyrimidinyl)-4-fluoro-, 1-methylethyl ester

HRID 2165801Notes

Reaction equation

HRID 2165801 reaction equation
Cl[CH:2]([F:4])[F:3].[Cl:5][C:6]1[CH:17]=[C:16]([F:18])[C:15]([N:19]2[C:24](=[O:25])[CH:23]=[C:22]([CH3:26])[NH:21][C:20]2=[O:27])=[CH:14][C:7]=1[C:8]([O:10][CH:11]([CH3:13])[CH3:12])=[O:9].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:5][C:6]1[CH:17]=[C:16]([F:18])[C:15]([N:19]2[C:24](=[O:25])[CH:23]=[C:22]([CH3:26])[N:21]([CH:2]([F:4])[F:3])[C:20]2=[O:27])=[CH:14][C:7]=1[C:8]([O:10][CH:11]([CH3:13])[CH3:12])=[O:9]

Participants

5

Reactant 3

HCID 6372ChlorodifluoromethaneHCID 11430Potassium CarbonateHCID 19994231HCID 19994231, compound

Product 1

HCID 135408Benzoic acid, 2-chloro-5-(3-(difluoromethyl)-3,6-dihydro-4-methyl-2,6-dioxo-1(2H)-pyrimidinyl)-4-fluoro-, 1-methylethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

103 g of chlorodifluoromethane are conducted into a suspension of 145.0 g of isopropyl 2-chloro-4-fluoro-5-[3,6-dihydro-2,6-dioxo-4-methyl-1(2H)-pyrimidinyl]-benzoate and 59.0 g of anhydrous, finely powdered potassium carbonate in 1 l of dimethylformamide for 6 hours while stirring at 80° C. After cooling the solid constituent is filtered off under suction and rinsed with 100 ml of dimethylformamide. The filtrate is concentrated to a large extent under reduced pressure at 55° C., the residue is poured into 2 l of water and the aqueous mixture is adjusted to pH 3 with concentrated hydrochloric acid. The mixture is extracted with 1.5 l of ethyl acetate and the organic phase is washed twice with 1 l of water each time. dried over anhydrous sodium sulphate and evaporated to dryness under reduced pressure. The resinous residue is purified by chromatography on a silica gel column using ethyl acetate/n-hexane (1:1) as the eluent. The product is dissolved in 1500 ml of hot n-hexane and the solution is treated with charcoal, filtered and concentrated to 700 ml at an elevated temperature. It is subsequently seeded and cooled to 5° C. while stirring. The resulting crystals are filtered off under suction, washed with n-hexane and dried. There is obtained isopropyl 2-chloro-5-[3-difluoromethyl-3,6-dihydro-2,6-dioxo-4-methyl-1(2H)-pyrimidinyl]-4-fluorobenzoate, m.p. 90°-93° C.

Workup

  1. temperatureAfter cooling the solid constituent
  2. filtrationis filtered off under suction
  3. washrinsed with 100 ml of dimethylformamide
  4. concentrationThe filtrate is concentrated to a large extent under reduced pressure at 55° C.
  5. additionthe residue is poured into 2 l of water
  6. extractionThe mixture is extracted with 1.5 l of ethyl acetate
  7. washthe organic phase is washed twice with 1 l of water each time
  8. dry with materialdried over anhydrous sodium sulphate
  9. customevaporated to dryness under reduced pressure
  10. customThe resinous residue is purified by chromatography on a silica gel column
  11. dissolutionThe product is dissolved in 1500 ml of hot n-hexane
  12. additionthe solution is treated with charcoal
  13. filtrationfiltered
  14. concentrationconcentrated to 700 ml at an elevated temperature
  15. temperaturecooled to 5° C.
  16. stirringwhile stirring
  17. filtrationThe resulting crystals are filtered off under suction
  18. washwashed with n-hexane
  19. customdried

Sources & evidence

ORD record
ord-b1d6af82d5614770b071a246e877bafe
Source dataset
uspto-grants-1990_07
Patent number
US04941909

Reaction notes

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