Methanol → HCID 66652424, compound

HRID 1844113Notes

Reaction equation

HRID 1844113 reaction equation
CC1(C)[O:9][C:7](=[O:8])[CH2:6][C:4](=[O:5])O1.[C:11]1([CH2:17][C:18](Cl)=O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CO[CH:23](OC)[N:24](C)C.CO>ClCCl>[O:5]=[C:4]1[C:17]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:18][NH:24][CH:23]=[C:6]1[C:7]([OH:9])=[O:8]

Participants

6

Reactant 4

HCID 887MethanolHCID 7679Phenylacetyl chlorideHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 78373Dimethylformamide dimethyl acetal

Product 1

HCID 66652424HCID 66652424, compoundYield 44.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of Meldrum's acid (1.0 g, 7.0 mmol) and dry TEA (5 mL, 35.6 mmol) in dry dichloromethane (15 mL) was added phenylacetyl chloride (0.95 mL, 7.13 mmol) dropwise at ice bath temperature. The reaction mixture was allowed to back to RT, stirred for 3.5 h. Crude adduct of Meldrum's acid and acetyl chloride was washed by 3N hydrochloric acid and concentrated. To the residue was added ethanol (20 mL); the reaction mixture was heated to reflux for 3 h. Resultant residue was made to react to N,N-dimethylformamide dimethyl acetal (1.5 mL, 11.2 mmol) in xylenes (15 mL) at 120° C. for 4 hrs with removal of methanol and concentrated in vacuo. The residue was cyclized by ammonium acetate (1.15 g) in methanol (20 mL) at reflux for 4 hrs. Crude ethyl ester was saponificated by 10% sodium hydroxide solution (10 mL) in methanol (20 mL). Reaction mixture was heated at 65° C. for 2.5 hours. Solid precipitated during acidic workup by 3N hydrochloric acid was collected by filter, washed by methanol (small amount), water and diethyl ether, dried to give the title compound D125 (671.2 mg, 21% over four steps). 1H-NMR (400 MHz, DMSO-d6): 13.16 (brs, 1H, NH), 8.60 (d, J=1.6 Hz, 1H, pyridone-H), 8.23 (d, J=1.6 Hz, 1H, pyridone-H), 7.65 (d, J=8 Hz, 2H, ArH), 7.50-7.41 (m, 3H, ArH).

Workup

  1. customto back to RT
  2. washCrude adduct of Meldrum's acid and acetyl chloride was washed by 3N hydrochloric acid
  3. concentrationconcentrated
  4. additionTo the residue was added ethanol (20 mL)
  5. temperaturethe reaction mixture was heated
  6. temperatureto reflux for 3 h
  7. concentrationconcentrated in vacuo
  8. temperatureat reflux for 4 hrs
  9. customReaction mixture
  10. customSolid precipitated during acidic workup by 3N hydrochloric acid
  11. customwas collected
  12. filtrationby filter
  13. washwashed by methanol (small amount), water and diethyl ether
  14. customdried

Sources & evidence

ORD record
ord-2a8de1e681784ef6bf35e9c20a333af5
Source dataset
uspto-grants-2015_02
Patent number
US08946282B2

Reaction notes

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