Ethanol → HCID 178470077, compound

HRID 2403263Notes

Reaction equation

HRID 2403263 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=O.[C:11]([OH:14])(=[O:13])[CH3:12].[F:15][C:16]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[C:17]=1[C:18]([NH2:20])=[NH:19].Cl.[CH2:28]([OH:30])C.[CH2:31](O)[CH3:32]>>[Cl:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]1[C:12]([C:11]([O:14][CH2:31][CH3:32])=[O:13])=[C:28]([OH:30])[NH:20][C:18]([C:17]2[C:16]([F:15])=[CH:24][C:23]([F:25])=[CH:22][C:21]=2[F:26])=[N:19]1

Participants

5

Reactant 4

HCID 702EthanolHCID 1450242-Chloro-4-fluorobenzaldehydeHCID 21887872Ethanol hydrochlorideHCID 67234591HCID 67234591, compound

Product 1

HCID 178470077HCID 178470077, compound

Procedure

25 mmol of Ethyl 4-chloroacetate, 25 mmol of 2-chloro-4-fluorobenzaldehyde and 30 mmol of 2,4,6-trifluorobenzamidine acetate were dissolved in 100 ml of anhydrous ethanol, 0.6 ml of hydrogen chloride/ethanol was added, and the mixture was subjected to reflux for 72 h. The mixture was then evaporated to remove the solvents, ethyl acetate and water were added, and the phases were separated. The layer of ethyl acetate was dried over anhydrous sodium sulfate and subjected to a column chromatography to give 1.42 g of a white crystal and 1.77 g of ethyl 4-(2-chloro-4-fluorophenyl)-2-(2,4,6-trifluorophenyl)-6-hydroxyl-1,4-dihydropyrimidine-5-carboxylate. 1.77 g (4 mmol) of ethyl 4-(2-chloro-4-fluorophenyl)-2-(2,4,6-trifluorophenyl)-6-hydroxyl-1,4-dihydropyrimidine-5-carboxylate was dissolved in dichloromethane, 10 mmol of thionyl chloride was added, and the mixture was subjected to reflux for 8 h to give 19.6 g of ethyl 2-(2,4,6-trifluorophenyl)-4-2-chloro-4-fluorophenyl)-6-(chloromethyl)-1,4-dihydropyrimidine-5-carboxylate (yield 29.4%): 1H-NMR (400 MHz, DMSO-d6) δ 1.07(3H, t, J=7.0 Hz, CH3); 4.76(2H, q, J=11.4 Hz, CH2); 3.99(2H, q, J=7.0 Hz, CH2); 6.02(1H, s, CH); 7.44-7.50(2H, m, ArH); 7.28-7.34(3H, m, ArH); 10.28(1H, br, NH). MS(FAB) 461.2 (M+).

Workup

  1. temperatureto reflux for 72 h
  2. customThe mixture was then evaporated
  3. customto remove the solvents, ethyl acetate and water
  4. additionwere added
  5. customthe phases were separated
  6. dry with materialThe layer of ethyl acetate was dried over anhydrous sodium sulfate

Sources & evidence

ORD record
ord-d9315074d0e94869ba0dc15bc2c56bbb
Source dataset
uspto-grants-2014_08
Patent number
US08802669B2

Reaction notes

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