Sodium hydride → 4-[2-Cyano-5-(3-thienylmethoxy)phenoxy]-4-(2-methylphenyl)butanoic acid

HRID 322889ノート

反応式

HRID 322889 の反応式
[OH:1][CH:2]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH3:14])[CH2:3][CH2:4][C:5]([O-:7])=[O:6].[Na+].[H-].[Na+].F[C:19]1[CH:26]=[C:25]([O:27][CH2:28][C:29]2[CH:33]=[CH:32][S:31][CH:30]=2)[CH:24]=[CH:23][C:20]=1[C:21]#[N:22]>O1CCCC1.Cl.C(OC(C)C)(C)C>[C:21]([C:20]1[CH:23]=[CH:24][C:25]([O:27][CH2:28][C:29]2[CH:33]=[CH:32][S:31][CH:30]=2)=[CH:26][C:19]=1[O:1][CH:2]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH3:14])[CH2:3][CH2:4][C:5]([OH:7])=[O:6])#[N:22]

参加物

7

反応物 3

HCID 24758Sodium hydrideHCID 107283302-Fluoro-4-(3-thienylmethoxy)benzonitrileHCID 23665160HCID 23665160、化合物

生成物 1

HCID 220102444-[2-Cyano-5-(3-thienylmethoxy)phenoxy]-4-(2-methylphenyl)butanoic acid

試薬・触媒・溶媒 3

HCID 313Hydrochloric Acid溶媒HCID 7914Diisopropyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A mixture of sodium 4-hydroxy-4-(2-methyl-phenyl)butanoate, thought to be the (R)-enantiomer, (3 g) and sodium hydride (1.5 g; 60% w/v dispersion in mineral oil; 37.5 mmol) in tetrahydrofuran (50 mL) is stirred at ambient temperature for 1 hour under an atmosphere of argon, and is then warmed to 55° C. It is then treated with 2-fluoro-4-(3-thienylmethoxy)benzonitrile (3 g), in one portion, and stirring is continued at 55° C. for 15 hours. The mixture is then cooled, diluted with hydrochloric acid (200 mL; 1 N) and extracted with ethyl acetate (4×100 mL). The combined extracts are dried over magnesium sulphate and concentrated in vacuo, to give an oily residue. This residue is boiled in isopropyl ether, and the resulting mixture is filtered while hot, and then allowed to cool. The yellow solid which separates is collected and recrystallized from a mixture of ethyl acetate and hexane, to give 4-[2-cyano-5-(3-thienylmethoxy)phenoxy]-4-(2-methylphenyl)butanoic acid, thought to be the (R)-enantiomer, (1.5 g) in the form of a white fluffy solid, m.p. 145° C. Chiral HPLC assay showed a 98% enantiomeric excess. [Elemental analysis:- C,67.82;H,5.18; N,3.24%; Calculated:- C,67.80;H,5.19;N,3.44%].

後処理

  1. temperatureis then warmed to 55° C
  2. stirringstirring
  3. waitis continued at 55° C. for 15 hours
  4. temperatureThe mixture is then cooled
  5. extractionextracted with ethyl acetate (4×100 mL)
  6. dry with materialThe combined extracts are dried over magnesium sulphate
  7. concentrationconcentrated in vacuo
  8. customto give an oily residue
  9. filtrationthe resulting mixture is filtered while hot, and
  10. temperatureto cool
  11. customThe yellow solid which separates is collected
  12. customrecrystallized from a mixture of ethyl acetate and hexane

出典と根拠

ORDレコード
ord-021ed2f4ee57410db6d005ebc2a2b7a3
出典データセット
uspto-grants-2001_04
特許番号
US06211234B1

反応ノート

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