Phenacyl bromide → HCID 59627907, compound

HRID 1367667Notes

Reaction equation

HRID 1367667 reaction equation
[C:1]([CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:4])[CH2:2][CH3:3].[H-].[Na+].Br[CH2:14][C:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:16].[Cl-].[NH4+]>C1COCC1>[CH2:9]([O:8][C:6](=[O:7])[CH:5]([CH2:14][C:15](=[O:16])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:1](=[O:4])[CH2:2][CH3:3])[CH3:10]

Participants

6

Reactant 4

HCID 6259Phenacyl bromideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 78656Ethyl 3-oxovalerate

Product 1

HCID 59627907HCID 59627907, compoundYield 81.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Ethyl propionylacetate (45) (10 g, 69.4 mmol) was added slowly to a stirred suspension of sodium hydride (60% dispersion in mineral oil, 3.33 g, 83.3 mmol, 1.2 equiv) in THF (100 ml) at 0° C. and the mixture was stirred for 30 min. 2-Bromoacetophenone 46a (15.2 g, 76.34 mmol, 1.1 equiv) in THF (10 ml) was added dropwise and the reaction mixture was stirred at room temperature for 16 h. Saturated aqueous ammonium chloride (60 ml) was added and the mixture was subsequently extracted with diethyl ether (3×70 ml). The combined organic layers were washed with brine and dried over anhydrous sodium sulfate. The solvent was removed in vacuo to give a dark yellow oil that was purified by flash column chromatography (EtOAc-hexane, 1:10) to give the diketoester 47a (14.8 g, 81%) as a yellow oil: TLC Rf=0.50 (silica gel, 25% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3) δ 7.98 (d, 3J=8.4 Hz, 2H), 7.58 (m, 1H), 7.46 (m, 2H), 4.18-4.25 (q, 3J=7.2 Hz, 3H), 3.70-3.3.79 (dd, 3J=8.4 Hz, 2J=18.4 Hz, 1H), 3.49-3.57 (dd, 3J=5.2 Hz, 2J=18.4 Hz, 1H), 2.70-2.91 (m, 2H), 1.26-1.31 (t, 3J=7.2 Hz, 3H), 1.10-1.15 (t, 3J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 205.42, 197.43, 169.26, 136.29, 133.63, 128.81, 128.31, 61.864, 53.20, 37.68, 36.55, 14.22, 7.84; HRMS calcd for C15H18O4+Na+ 285.1103; found 285.1093 [M+Na+].

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 16 h
  2. extractionthe mixture was subsequently extracted with diethyl ether (3×70 ml)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. customThe solvent was removed in vacuo
  6. customto give a dark yellow oil that
  7. customwas purified by flash column chromatography (EtOAc-hexane, 1:10)

Sources & evidence

ORD record
ord-26834d0442b64bcbb5978ecce8457d66
Source dataset
uspto-grants-2011_02
Patent number
US07893268B2

Reaction notes

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