Hydrochloric Acid → HCID 178501816, compound

HRID 2368794Notes

Reaction equation

HRID 2368794 reaction equation
CC(C)([O-])C.[Na+].[C:7]([O:13][CH3:14])(=[O:12])[C:8]([O:10]C)=O.[C:15]([C:18]1[C:19](=[O:41])[N:20]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[F:40])[CH:21]=[C:22]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][C:26]=2[F:32])[CH:23]=1)(=[O:17])[CH3:16].Cl>C1COCC1>[F:32][C:26]1[CH:27]=[C:28]([F:31])[CH:29]=[CH:30][C:25]=1[CH2:24][C:22]1[CH:23]=[C:18]([C:15](=[O:17])[CH:16]=[C:8]([OH:10])[C:7]([O:13][CH3:14])=[O:12])[C:19](=[O:41])[N:20]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[F:40])[CH:21]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11120Dimethyl oxalateHCID 23676156Sodium t-butoxideHCID 67261221HCID 67261221, compound

Product 1

HCID 178501816HCID 178501816, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of sodium t-butoxide (4.49 g, 45.3 mmol) in anhydrous THF (230 ml) was added dimethyl oxalate (5.41 g, 45.3 mmol) in anhydrous THF (60 ml) under argon condition. The mixture was stirred at room temperature for 30 min and a solution of 3-acetyl-5-(2,4-difluorobenzyl)-1-(2-fluorobenzyl)pyridin-2(1H)-one 6 (4.21 g, 11.3 mmol) in THF (60 ml) was added. The reaction mixture was stirred at room temperature for 3 h and then cooled in ice bath, and then 1N HCl (230 ml) was added in one portion. The crude product was extracted with ethyl acetate (2×230 ml). The combined organic layers were washed with saturated brine (2×230 ml) and ethyl acetate was distilled off to give a brown residue, which was triturated with methanol. The product was obtained by vacuum filtration. Yield 2.59 g (50%). 1H NMR (CDCl3, 500 MHz): δ 8.18 (d, 1H, J=3.1 Hz), 7.89 (s, 1H), 7.53 (s, 1H), 7.49-7.46 (s, 1H), 7.35-7.31 (s, 1H), 7.16-7.07 (m, 3H), 6.87-6.80 (m, 2H), 5.20 (s, 2H), 3.90 (s, 3H), 3.75 (s, 2H). 13C NMR (CDCl3, 125 MHz): δ 185.0, 171.9, 162.8, 162.6, 162.2, 160.6, 160.2, 159.6, 144.8, 142.0, 131.7, 131.2, 130.6, 124.8, 123.6, 122.4, 121.9, 117.7, 115.7, 111.7, 104.3, 101.8, 53.2, 47.6, 30.6.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 3 h
  2. temperaturecooled in ice bath
  3. extractionThe crude product was extracted with ethyl acetate (2×230 ml)
  4. washThe combined organic layers were washed with saturated brine (2×230 ml) and ethyl acetate
  5. distillationwas distilled off
  6. customto give a brown residue, which
  7. customwas triturated with methanol
  8. customThe product was obtained by vacuum filtration

Sources & evidence

ORD record
ord-9f1ebe50bd9f41cfa19a524f6d70cc72
Source dataset
uspto-grants-2014_04
Patent number
US08703801B2

Reaction notes

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