Hydrochloric Acid → Ethyl 4-(3-chlorophenyl)-2,4-dioxobutanoate

HRID 920854Notes

Reaction equation

HRID 920854 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[C:11](OCC)(=[O:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13].[H-].[Na+].Cl>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH2:9][C:11](=[O:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7268Diethyl OxalateHCID 149331-(3-Chlorophenyl)ethanoneHCID 24758Sodium hydride

Product 1

HCID 11054223Ethyl 4-(3-chlorophenyl)-2,4-dioxobutanoate

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To an ice-cold solution of 1-(3-chlorophenyl)ethanone (16.79 mL, 129 mmol) and diethyl oxalate (18.05 mL, 136 mmol) in DMF (78.0 mL) was added, portionwise over 30 min., NaH (6.09 g, 155 mmol, 60% dispersion in mineral oil) and the resultant mixture was stirred at that temperature for 20 min. and then at room temperature for 16 h. The reaction mixture was diluted with water and acidified to pH=4-5 with 1N aq. HCl. The mixture was further diluted with copious amounts of water. The aq. layer was extracted with EtOAc (4×100 mL) and the combined organic layer was washed with water, brine, dried over anhydrous MgSO4, filtered and the filtrate was concentrated under reduced pressure to provide a crude residue. It was purified by silica gel chromatography (220 g REDISEP® column, eluting with a 0 to 15% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate A1C (27.1 g, 84%) as a solid. MS(ES): m/z=277.10 [M+Na]+; 1H NMR (400 MHz, chloroform-d) δ ppm 7.99 (t, J=1.8 Hz, 1H), 7.95-7.86 (m, 1H), 7.60 (ddd, J=8.0, 2.1, 1.0 Hz, 1H), 7.48 (t, J=7.9 Hz, 1H), 7.06 (s, 1H), 4.43 (q, J=7.3 Hz, 2H), 1.44 (t, J=7.2 Hz, 3H).

Workup

  1. extractionThe aq. layer was extracted with EtOAc (4×100 mL)
  2. washthe combined organic layer was washed with water, brine
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-637a2287b54b4d2bae2a72057f090ccd
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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