3-Fluorobenzaldehyde → 6-(2-Chlorophenyl)-5-(4-chlorophenyl)-3-[3-(3-fluorophenyl)-3-hydroxypropanoyl]pyridin-2(3H)-one

HRID 1673220Notes

Reaction equation

HRID 1673220 reaction equation
[C:1]([C:4]1[C:5](=[O:24])[NH:6][C:7]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:23])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)[CH:9]=1)(=[O:3])[CH3:2].[F:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][CH:33]=1)[CH:29]=[O:30].C[O-].[Na+]>C1COCC1.CO.CCOC(C)=O>[Cl:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C:7]1[C:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)=[CH:9][CH:4]([C:1](=[O:3])[CH2:2][CH:29]([C:28]2[CH:31]=[CH:32][CH:33]=[C:26]([F:25])[CH:27]=2)[OH:30])[C:5](=[O:24])[N:6]=1

Participants

7

Reactant 3

HCID 680093-FluorobenzaldehydeHCID 10942334Sodium MethoxideHCID 670199153-Acetyl-6-(2-chlorophenyl)-5-(4-chlorophenyl)pyridin-2(1H)-one

Product 1

HCID 670199346-(2-Chlorophenyl)-5-(4-chlorophenyl)-3-[3-(3-fluorophenyl)-3-hydroxypropanoyl]pyridin-2(3H)-one

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the product of Example 4, Step A (0.5 g, 1.4 mmol) in THF (3 mL) and MeOH (1.5 mL) was added 3-fluorobenzaldehyde (0.6 mL, 2.8 mmol) and NaOMe (0.2 g, 0.56 mmol). The reaction was stirred at rt overnight, followed by heating at 50° C. for an additional day. The reaction was diluted with EtOAc and washed with saturated aq NaHCO3, brine, dried (Na2SO4), filtered and concentrated The residue was purified by flash chromatography on silica gel gradient eluted with 0-30% EtOAc in hexane to afford the product.

Workup

  1. temperatureby heating at 50° C. for an additional day
  2. washwashed with saturated aq NaHCO3, brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated The residue
  6. customwas purified by flash chromatography on silica gel gradient
  7. washeluted with 0-30% EtOAc in hexane
  8. customto afford the product

Sources & evidence

ORD record
ord-a9c8fd6f2ece437b919566058546820d
Source dataset
uspto-grants-2011_08
Patent number
US07999107B2

Reaction notes

Loading…