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

HRID 322904노트

반응식

HRID 322904 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
57.5 °C

실험 절차

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%]

후처리

  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

출처 및 근거

ORD 기록
ord-679a2a5cfb1b4d3c91ea42c2fed92847
출처 데이터셋
uspto-grants-2001_04
특허 번호
US06211234B1

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