D-Alanine,N-[3-chloro-4-(trifluoromethyl)phenyl]- → (R)-2-(3-Chloro-4-trifluoromethyl-phenylamino)-propan-1-ol

HRID 2095504ノート

反応式

HRID 2095504 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([NH:12][C@H:13]([CH3:17])[C:14](O)=[O:15])[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:12][C@H:13]([CH3:17])[CH2:14][OH:15])[CH:5]=[CH:6][C:7]=1[C:8]([F:11])([F:10])[F:9]

参加物

3

反応物 1

HCID 66783571D-Alanine,N-[3-chloro-4-(trifluoromethyl)phenyl]-

生成物 1

HCID 67074173(R)-2-(3-Chloro-4-trifluoromethyl-phenylamino)-propan-1-ol収率 93.3%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

20.55 ml (20.55 mmol, 1 M in THF) of a borane-tetrahydrofuran complex solution was added dropwise at 0° C. to a solution of 2.20 g (8.20 mmol) of (R)-2-(3-chloro-4-trifluoromethyl-phenylamino)-propionic acid (22% ee) in 33 ml THF, then after 10 min the ice bath was removed and the solution stirred for 2.5 h at RT. After cooling, 14 ml of MeOH and 0.7 ml of H2SO4 were added, and after 30 min at RT and 1 h at reflux the reaction mixture was concentrated in vacuo. The residue was partitioned between 1 M aq. sodium hydroxide saturated with NaCl solution and EtOAc (3×). The organic layer was washed with brine, dried (Na2SO4), filtered, and evaporated. Flash silica gel column (CH2Cl2/MeOH 99:1) afforded 1.94 g (93%) of the title compound as a 61:39 mixture of the (R) and (S) stereoisomers as yellow oil. MS: 252.04 (M−H−, Cl)

後処理

  1. customafter 10 min the ice bath was removed
  2. temperatureAfter cooling
  3. addition14 ml of MeOH and 0.7 ml of H2SO4 were added
  4. waitafter 30 min at RT
  5. temperature1 h at reflux the reaction mixture
  6. concentrationwas concentrated in vacuo
  7. customThe residue was partitioned between 1 M aq. sodium hydroxide saturated with NaCl solution and EtOAc (3×)
  8. washThe organic layer was washed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated

出典と根拠

ORDレコード
ord-ef0d0dd8bbd24c10ba1745df8beb7670
出典データセット
uspto-grants-2013_05
特許番号
US08445674B2

反応ノート

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