Ethanol → HCID 59612092, compound

HRID 889644Notes

Reaction equation

HRID 889644 reaction equation
[Na].C(O)C.[Cl:5][C:6]1[CH:11]=[CH:10][C:9](/[CH:12]=[CH:13]/[C:14](=[O:16])[CH3:15])=[C:8]([F:17])[CH:7]=1.[C:18](OCC)(=[O:24])[C:19]([O:21][CH2:22][CH3:23])=[O:20]>CCOCC>[CH2:22]([O:21][C:19](=[O:20])[C:18](=[O:24])[CH2:15][C:14](=[O:16])/[CH:13]=[CH:12]/[C:9]1[CH:10]=[CH:11][C:6]([Cl:5])=[CH:7][C:8]=1[F:17])[CH3:23]

Participants

6

Reactant 4

HCID 702EthanolHCID 7268Diethyl OxalateHCID 5360545Sodium2×HCID 59612093HCID 59612093, compound

Product 1

HCID 59612092HCID 59612092, compoundYield 86.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
-5 °C

Procedure

Sodium pellets (2.88 g, 0.125 mol) were slowly added to absolute ethyl alcohol (EtOH, 125 mL). After the sodium had reacted, the solvent was removed under reduced pressure, and anhydrous ether (200 mL) was added. The reaction mixture was cooled to −5° C., and a solution of (E)-4-(4-chloro-2-fluorophenyl)-but-3-en-2-one (1; 24.75 g, 0.125 mol) and diethyl oxalate (21.9 g, 0.15 mol) in anhydrous ether (25 mL) was added over 30 min. After stirring 2 days (d) at room temperature, the yellow solid was filtered and washed with ether. After 1 hour (h) of drying at room temperature, the solid was partitioned between CH2Cl2 (200 mL) and 1 N sulfuric acid (H2SO4, 150 mL). The organic layer was dried (MgSO4), and the solvent was removed to give (E)-6-(4-chloro-2-fluoro-phenyl)-2,4-dioxo-hex-5-enoic acid ethyl ester (3; 32.3 g, 86%) as a yellow solid. A small sample was recrystallized from EtOH to yield yellow crystals: mp 84-85° C.; 1H NMR (400 MHz, CDCl3) δ 14.72 (s, 1H), 7.76 (d, J=16.1 Hz, 1H), 7.49 (d, J=8.3 Hz, 1H), 7.24-7.12 (m, 2H), 6.73 (d, J=16.1 Hz, 1H), 6.53 (s, 1H), 4.38 (q, J=7.1 Hz, 2H), 1.40 (t, J=7.1 Hz, 3H); HRMS-ESI (m/z): calcd for C14H12ClFO4, 298.041. found, 298.041.

Workup

  1. customthe solvent was removed under reduced pressure, and anhydrous ether (200 mL)
  2. additionwas added
  3. filtrationthe yellow solid was filtered
  4. washwashed with ether
  5. customAfter 1 hour (h) of drying at room temperature
  6. customthe solid was partitioned between CH2Cl2 (200 mL) and 1 N sulfuric acid (H2SO4, 150 mL)
  7. dry with materialThe organic layer was dried (MgSO4)
  8. customthe solvent was removed

Sources & evidence

ORD record
ord-2c5120c9dff7450bbdf0343101f8111b
Source dataset
uspto-grants-2012_08
Patent number
US08252938B2

Reaction notes

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