Tetrahydrofuran → 3-[[(3-Phenoxyphenyl)-(3,3,3-trifluoro-2-hydroxypropyl)amino]methyl]benzenemethanol

HRID 991334ノート

反応式

HRID 991334 の反応式
[O:1]([C:8]1[CH:9]=[C:10]([N:14]([CH2:22][C:23]2[CH:24]=[C:25]([CH:30]=[CH:31][CH:32]=2)[C:26](OC)=[O:27])[CH2:15][CH:16]([OH:21])[C:17]([F:20])([F:19])[F:18])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C1COCC1>ClCCl.C(OCC)(=O)C>[O:1]([C:8]1[CH:9]=[C:10]([N:14]([CH2:22][C:23]2[CH:24]=[C:25]([CH2:26][OH:27])[CH:30]=[CH:31][CH:32]=2)[CH2:15][CH:16]([OH:21])[C:17]([F:18])([F:19])[F:20])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

6

反応物 3

HCID 8028Tetrahydrofuran2 回HCID 10993963Methyl 3-(((3-phenoxyphenyl)(3,3,3-trifluoro-2-hydroxypropyl)amino)methyl)benzoateHCID 21226445Aluminium lithium hydride2 回

生成物 1

HCID 235060063-[[(3-Phenoxyphenyl)-(3,3,3-trifluoro-2-hydroxypropyl)amino]methyl]benzenemethanol収率 54%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒2 回

反応条件

温度
-40 °C

実験手順

To a solution of methyl 3-[[(3-phenoxyphenyl)(3,3,3-trifluoro-2-hydroxy-propyl)amino]methyl]benzoate (197 mg, 0.00044 mol) in 2.0 mL of dichloromethane at −40° C. was slowly added a 1.0 M solution of lithium aluminum hydride in THF (1.1 mL, 0.0011 mol). The reaction mixture was stirred at −40° C. for 1 h, then diluted with ethyl acetate and quenched with water. The organic layer was dried over MgSO4 and concentrated in vacuo. The crude material was determined to contain a significant amount of unreacted starting material by HPLC at this stage. The crude material was resubjected to the reaction conditions using 2 mL of anhydrous tetrahydrofuran and 1.0 M lithium aluminum hydride (1.3 mL, 0.0013 mol) at −40° C. for 1 h, then diluted with ethyl acetate and quenched with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried over MgSO4 and concentrated in vacuo. The crude product was purified by column chromatography on silica gel eluting with 2:3 ethyl acetate:hexane to afford 99 mg (54%) of the desired 3-[[(3-phenoxyphenyl)-(3,3,3-trifluoro-2-hydroxypropyl)amino]methyl]benzenemethanol product as a white solid. Anal. calcd. for C23H22F3NO3: C, 66.18; H, 5.31; N, 3.36. Found: C, 65.98; H, 5.39; N, 3.22. HRMS calcd. 418.1630 [M+H]+, found: 418.1636. 1H NMR (C6D6) δ 7.08-6.92 (m, 8H), 6.89-6.80 (m, 2H), 6.56 (s, 1H), 6.46 (d, 1H), 6.38 (d, 1H), 4.26 (s, 2H), 4.21 (d, 2H), 3.77 (appq, 1H), 3.52 (d, 1H), 1.92 (bs, 1H), 0.96 (bs, 1H). 19F NMR (C6D6) δ −78.91 (d, 3F).

後処理

  1. customquenched with water
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe crude material was resubjected to the reaction conditions
  5. customat −40° C.
  6. customfor 1 h
  7. customquenched with water
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. dry with materialthe combined organic layers were dried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by column chromatography on silica gel eluting with 2:3 ethyl acetate

出典と根拠

ORDレコード
ord-c2625b05b3cb450db210524a78242a8d
出典データセット
uspto-grants-2002_10
特許番号
US06462092B1

反応ノート

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