Sodium hydride → HCID 53853519, compound

HRID 322976Notes

Reaction equation

HRID 322976 reaction equation
[OH:1][C:2]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[CH:16]=[CH:15][S:14][CH:13]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[H-].[Na+].Cl[CH:20]([C:28]1[CH:33]=[C:32]([CH3:34])[CH:31]=[CH:30][C:29]=1[CH3:35])[CH2:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24]>CN(C=O)C>[C:4]([C:3]1[CH:6]=[CH:7][C:8]([O:10][CH2:11][C:12]2[CH:16]=[CH:15][S:14][CH:13]=2)=[CH:9][C:2]=1[O:1][CH:20]([C:28]1[CH:33]=[C:32]([CH3:34])[CH:31]=[CH:30][C:29]=1[CH3:35])[CH2:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])#[N:5]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10657149HCID 10657149, compoundHCID 54337869HCID 54337869, compound

Product 1

HCID 53853519HCID 53853519, compoundYield 17.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Hydroxy-4-(3-thienylmethoxy)benzonitrile (1.5 g) is added portionwise to a stirred suspension of sodium hydride (440 mg, 60% dispersion in mineral oil) in dry DMF(50 mL). After stirring at ambient temperature for 30 minutes, ethyl (RS)-4-chloro-4-(2,5-dimethylphenyl)butanoate (2.5 g) is added in one portion and the reaction stirred for 48 hours at 90° C. The reaction is concentrated in vacuo and the residue partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer is extracted twice with ethyl acetate (50 mL). The combined organic phases are dried over magnesium sulphate, filtered and concentrated in vacuo. The residue is purified by flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (1:2 v/v). Fractions homogeneous in the required product are combined and evaporated to give ethyl (RS)-4-(2-cyano-5-(3-thienylmethoxy)phenoxy)-4-(2,5-dimethylphenyl)butanoate (500 mg) as a pale brown oil.

Workup

  1. stirringthe reaction stirred for 48 hours at 90° C
  2. concentrationThe reaction is concentrated in vacuo
  3. customthe residue partitioned between ethyl acetate (50 mL) and water (50 mL)
  4. extractionThe aqueous layer is extracted twice with ethyl acetate (50 mL)
  5. dry with materialThe combined organic phases are dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by flash chromatography on silica eluting with a mixture of ethyl acetate and pentane (1:2 v/v)
  9. customevaporated

Sources & evidence

ORD record
ord-ab5292075f4e4004b11a47f8526311d0
Source dataset
uspto-grants-2001_04
Patent number
US06211234B1

Reaction notes

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