Hydrochloric Acid → Ethyl 3-(4-Fluorophenyl)-3-Oxopropanoate

HRID 1776933Notes

Reaction equation

HRID 1776933 reaction equation
[C:1](=[O:8])([O:5][CH2:6][CH3:7])OCC.[H-].[Na+].[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18](=[O:20])[CH3:19])=[CH:14][CH:13]=1.Cl>O1CCCC1>[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18](=[O:20])[CH2:19][C:1]([O:5][CH2:6][CH3:7])=[O:8])=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7766Diethyl CarbonateHCID 98284'-FluoroacetophenoneHCID 24758Sodium hydride

Product 1

HCID 2758844Ethyl 3-(4-Fluorophenyl)-3-OxopropanoateYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Diethyl carbonate (130 g, 1.1 mol) was dissolved in a suspension of NaH (60% in oil, 50.2 g, 1.3 mol) in anhydrous tetrahydrofuran (1.5 L), and then 1-(4-fluorophenyl)ethanone (150 g, 1.09 mol) was added dropwise at 70° C. The resulting mixture was stirred at 70° C. for 3 hours. After the reaction mixture was cooled to room temperature and poured into HCl (1 N). The mixture was extracted with EtOAc, the organic phase was dried with anhydrous NaSO4 and concentrated in vacuo. The resulting residue was purified using column chromatography (eluted with petroleum ether/EtOAc=50/1) to provide ethyl 3-(4-fluorophenyl)-3-oxopropanoate (217 g, yield: 95%). 1H-NMR (CDCl3, 400 MHz) δ 7.92˜7.97 (m, 2H), 7.07˜7.13 (m, 2H), 4.14˜4.20 (m, 2H), 3.93 (s, 2H), 1.22 (d, J=7.2 Hz, 3H). MS (M+H)+: 211.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. extractionThe mixture was extracted with EtOAc
  3. dry with materialthe organic phase was dried with anhydrous NaSO4
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified
  6. washcolumn chromatography (eluted with petroleum ether/EtOAc=50/1)

Sources & evidence

ORD record
ord-c3a581825d4641908baf54dfddbafa65
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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