Sodium hydride → 3-Oxo-2-(2-oxo-2-pyridin-2-yl-ethyl)-pentanoic Acid Ethyl Ester

HRID 2088397Notes

Reaction equation

HRID 2088397 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][C:20](C)=[CH:19][N: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][N:18]=1)[C:1](=[O:4])[CH2:2][CH3:3])[CH3:10]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 78656Ethyl 3-oxovalerateHCID 178014772-Bromo-1-(5-methyl-2-pyridyl)ethanone

Product 1

HCID 672674043-Oxo-2-(2-oxo-2-pyridin-2-yl-ethyl)-pentanoic Acid Ethyl EsterYield 79.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Ethyl propionylacetate 18 (5 g, 34.7 mmol) was added slowly to a stirred suspension of sodium hydride (60% dispersion in mineral oil, 1.665 g, 41.65 mmol, 1.2 equiv) in THF (50 ml) at 0° C. and the mixture was stirred for 30 min. Compound 19b (8.092 g, 38.17 mmol, 1.1 equiv) in THF (5 ml) was added dropwise and the reaction mixture was stirred at room temperature for 16 h. Saturated aqueous ammonium chloride (30 ml) was added and the mixture was subsequently extracted with diethyl ether (3×30 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 (10% EtOAc/hexanes) to give the diketoester 20b (7.3 g, 76%) as a yellow oil: TLC Rf=0.33 (silica gel, 20% EtOAc/hexane); 1H NMR (400 MHz, CDCl3) δ 8.50 (broad s, 1H), 7.89 (d, J=8.0 Hz, 1H), 7.66 (dd, J=1.6 Hz, 8.0 Hz, 1H), 4.20 (q, J=7.2 Hz, 2H), 4.15 (dd, J=6.0 Hz, 8.0 Hz, 1H), 3.92 (dd, J=8.4 Hz, 18.8 Hz, 1H), 3.74 (dd, J=6.0 Hz, 18.8 Hz, 1H), 2.85-2.66 (m, 2H), 2.41 (s, 3H), 1.27 (t, J=7.2 Hz, 3H), 1.10 (t, J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 205.5, 198.9, 169.6, 150.7, 149.8, 138.1, 137.3, 121.7, 61.8, 53.5, 37.1, 36.2, 18.9, 14.2, 7.9; HRMS calcd for C15H19NO4+Na+ 300.1212; found 300.1200 [M+Na+].

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 16 h
  2. extractionthe mixture was subsequently extracted with diethyl ether (3×30 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 (10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-1fb130899b74419a9081bd23275f2831
Source dataset
uspto-grants-2013_05
Patent number
US08435983B2

Reaction notes

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