Sodium hydride → HCID 68577361, compound

HRID 272927Notes

Reaction equation

HRID 272927 reaction equation
C[O:2][C:3](=O)[CH2:4][CH2:5][C:6]([C:28]#[N:29])([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][CH2:22][N:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:15][CH:14]=1)[CH2:7][CH2:8][C:9]([O:11][CH3:12])=[O:10].[H-].[Na+]>COCCOC>[CH3:12][O:11][C:9]([CH:8]1[CH2:7][C:6]([C:28]#[N:29])([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][CH2:22][N:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:15][CH:14]=2)[CH2:5][CH2:4][C:3]1=[O:2])=[O:10]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 68578752HCID 68578752, compound

Product 1

HCID 68577361HCID 68577361, compoundYield 81.4%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of 4-cyano-4-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]-heptanedioic acid dimethyl ester (8.8 g, 21.1 mmol) in 1,2-dimethoxyethane (176 mL) was charged portions of NaH (60% dispersion, 2.55 g, 63.4 mmol). The reaction mixture was heated to reflux. After 4.5 hr, the ¾ of solvent were evaporated and the mixture cooled to 20° C. with an ice bath and quenched with water (100 mL), HCl 1N (100 mL). The aqueous layer was extracted with ether (100 mL). After basification with NaOH the aqueous phases were extracted with dichloromethane. The combined organics were washed with water, dried over Na2SO4, filtrered and concentrated to provide 5-cyano-2-oxo-5-[4-(3-pyrrolidin-1-ylpropoxy)-phenyl]-cyclohexane-carboxylic acid methyl ester (6.6 g, 81%) as an oil. 1H NMR (400 MHz, CDCl3) δ12.2 (bs, 1H); 7.33 (d, 2H); 6.95 (d, 2H); 4.08-4.00 (m, 2H); 3.75 (s, 3H); 2.95 (d, 1H); 2.80-2.70 (m, 1H); 2.65-2.60 (m, 2H); 2.50-2.42 (m, 6H); 2.30-2.15 (m, 2H); 2.05-1.95 (m, 2H); 1.90-1.85 (m, 4H).

Workup

  1. temperatureThe reaction mixture was heated to reflux
  2. customthe ¾ of solvent were evaporated
  3. customquenched with water (100 mL), HCl 1N (100 mL)
  4. extractionThe aqueous layer was extracted with ether (100 mL)
  5. extractionAfter basification with NaOH the aqueous phases were extracted with dichloromethane
  6. washThe combined organics were washed with water
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-1c9ffff41b8246649bcb9384cd933a79
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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