Ethoxalyl chloride → HCID 10081833, compound

HRID 2202125Notes

Reaction equation

HRID 2202125 reaction equation
Cl[C:2](=[O:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[Br-].[F:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15][Zn+])=[CH:13][CH:12]=1>O1CCCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15][C:2](=[O:8])[C:3]([O:5][CH2:6][CH3:7])=[O:4])=[CH:13][CH:12]=1

Participants

5

Reactant 2

HCID 20884Ethoxalyl chlorideHCID 178505763HCID 178505763, compound

Product 1

HCID 10081833HCID 10081833, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of ethyl 2-chloro-2-oxoacetate (35 g, 256.35 mmol, 1.00 equiv) and Pd(PPh3)2Cl2 (9 g, 12.82 mmol, 0.05 equiv) in tetrahydrofuran (200 mL) maintained under nitrogen at 0° C. was added dropwise a solution of (4-fluorobenzyl)zinc(II) bromide (65 g, 255.47 mmol, 1.00 equiv) in tetrahydrofuran (500 mL). The reaction mixture was refluxed for 12 h then cooled to 0° C. and quenched by dropwise addition of 500 mL of saturated NH4Cl solution. The resulting mixture was extracted with 2×500 mL of ethyl acetate. The combined organic layers was washed with 1×1 L of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 0-5% of ethyl acetate in petroleum ether to give 18 g (34%) of ethyl 3-(4-fluorophenyl)-2-oxopropanoate as a yellow oil. 1H-NMR (300 MHz, DMSO): δ 7.36-7.33 (m, 2H), 7.18-7.12 (m, 2H), 4.50 (s, 1H), 4.26 (q, J=7.0 Hz, 2H), 1.20 (t, J=7.2 Hz, 3H) ppm.

Workup

  1. temperatureThe reaction mixture was refluxed for 12 h
  2. temperaturethen cooled to 0° C.
  3. customquenched by dropwise addition of 500 mL of saturated NH4Cl solution
  4. extractionThe resulting mixture was extracted with 2×500 mL of ethyl acetate
  5. washThe combined organic layers was washed with 1×1 L of brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified on a silica gel column
  9. washeluted with 0-5% of ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-2b36360f79a146cfbfbc088c2ed12b7f
Source dataset
uspto-grants-2016_06
Patent number
US09365527B2

Reaction notes

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