Diethyl Ether → 3-Methyl-2-oxo-4-pyridin-2-yl-cyclopent-3-enecarboxylic acid ethyl ester

HRID 2088398Notes

Reaction equation

HRID 2088398 reaction equation
[CH2:1]([O:3][C:4](=[O:19])[CH:5]([CH2:10][C:11](=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)[C:6](=[O:9])[CH2:7][CH3:8])[CH3:2].[OH-].[Na+].CCOCC>C(O)C>[CH2:1]([O:3][C:4]([CH:5]1[CH2:10][C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[C:7]([CH3:8])[C:6]1=[O:9])=[O:19])[CH3:2]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 672674043-Oxo-2-(2-oxo-2-pyridin-2-yl-ethyl)-pentanoic Acid Ethyl Ester

Product 1

HCID 672674453-Methyl-2-oxo-4-pyridin-2-yl-cyclopent-3-enecarboxylic acid ethyl esterYield 77.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A solution of the diketoester 20b (3.1 g, 11.19 mmol) in dry ethanol (35 ml) was added dropwise to a solution of sodium hydroxide (0.447 g, 11.19 mmol) in dry ethanol (15 ml) with vigorous stirring. The solution was stirred at room temperature overnight. Ether (200 ml) was added and the organic phase was washed with 2 N HCl (3×100 ml). The aqueous layer was cooled to 0° C. and made slightly basic by addition of sodium bicarbonate. The aqueous layer was then extracted with ethyl acetate (3×300 ml) and the organic phase was dried over anhydrous sodium sulfate. The solvent was removed in vacuo to give an oil that was purified by flash column chromatography (EtOAc/hexanes, 1:10) to give the cyclic β-ketoester 21b (2.115 g, 73%) as a yellow oil: TLC Rf=0.35 (silica gel, 33% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 7.62-7.60 (m, 1H), 7.54-7.52 (m, 1H), 4.24 (q, J=7.2 Hz, 2H), 3.56 (dd, J=2.8 Hz, 7.2 Hz, 1H), 3.42-3.25 (m, 2H), 2.41 (s, 3H), 2.12 (s, 3H), 1.31 (t, J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 203.2, 169.5, 164.4, 151.4, 150.6, 136.8, 136.5, 134.2, 123.3, 61.7, 51.1, 32.5, 18.6, 14.3, 10.6; HRMS calcd for C15H17NO3+Na+ 282.1106; found 282.1109 [M+Na+].

Workup

  1. washthe organic phase was washed with 2 N HCl (3×100 ml)
  2. temperatureThe aqueous layer was cooled to 0° C.
  3. additionmade slightly basic by addition of sodium bicarbonate
  4. extractionThe aqueous layer was then extracted with ethyl acetate (3×300 ml)
  5. dry with materialthe organic phase was dried over anhydrous sodium sulfate
  6. customThe solvent was removed in vacuo
  7. customto give an oil that
  8. customwas purified by flash column chromatography (EtOAc/hexanes, 1:10)

Sources & evidence

ORD record
ord-a1f49662ac6f4f5ba4840541ce10f0ac
Source dataset
uspto-grants-2013_05
Patent number
US08435983B2

Reaction notes

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