Sodium hydride → (RS)-4-(benzo[1,3]dioxol-4-yl)-4-[2-cyano-5-(3-pyridylmethoxy)phenoxy]butanoic acid

HRID 322904

Reaction equation

HRID 322904 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([CH:10]([OH:16])[CH2:11][CH2:12][C:13]([O-:15])=[O:14])[C:4]=2[O:3][CH2:2]1.[Na+].[H-].[Na+].F[C:21]1[CH:28]=[C:27]([O:29][CH2:30][C:31]2[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=2)[CH:26]=[CH:25][C:22]=1[C:23]#[N:24]>O1CCCC1>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[C:9]([CH:10]([O:16][C:25]3[CH:26]=[C:27]([O:29][CH2:30][C:31]4[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=4)[CH:28]=[CH:21][C:22]=3[C:23]#[N:24])[CH2:11][CH2:12][C:13]([OH:15])=[O:14])[C:4]=2[O:3][CH2:2]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 220104982-Fluoro-4-(3-pyridylmethoxy)benzonitrileHCID 86756589sodium (RS)-4-(benzo[1,3]dioxol-4-yl)-4-hydroxybutanoate

Product 1

HCID 22010433(RS)-4-(benzo[1,3]dioxol-4-yl)-4-[2-cyano-5-(3-pyridylmethoxy)phenoxy]butanoic acidYield 39.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
57.5 °C

Procedure

A solution of sodium (RS)-4-(benzo[1,3]dioxol-4-yl)-4-hydroxybutanoate (1.23 g) is added to a stirred suspension of sodium hydride (0.6 g, 60% dispersion in mineral oil) in tetrahydrofuran (50 mL). The mixture is stirred at room temperature for 1.5 hours when 2-fluoro-4-(3-pyridylmethoxy)benzonitrile (1.07 g) is added in one portion. The reaction mixture is heated at 55-60° C. for 18 hours and evaporated. The residue is dissolved in water (100 mL), the solution acidified to pH 2 with 1 N hydrochloric acid and the mixture extracted with ethyl acetate (100 mL). The organic phase is washed with water (100 mL), with brine (100 mL), dried over magnesium sulphate and evaporated. The yellow semi-solid residue is recrystallised from acetonitrile to give (RS)-4-(benzo[1,3]dioxol-4-yl)-4-[2-cyano-5-(3-pyridylmethoxy)phenoxy]butanoic acid (0.80 g) as a cream solid, m.p. 181-183° C. [Elemental analysis:- C,66.32; H,4.57; N,6.52%. Calculated :- C,66.66; H,4.66; N,6.48%]

Workup

  1. additionis added in one portion
  2. customevaporated
  3. dissolutionThe residue is dissolved in water (100 mL)
  4. extractionthe mixture extracted with ethyl acetate (100 mL)
  5. washThe organic phase is washed with water (100 mL), with brine (100 mL)
  6. dry with materialdried over magnesium sulphate
  7. customevaporated
  8. customThe yellow semi-solid residue is recrystallised from acetonitrile

Sources & evidence

ORD record
ord-679a2a5cfb1b4d3c91ea42c2fed92847
Source dataset
uspto-grants-2001_04
Patent number
US06211234B1

Linked notes

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