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

HRID 2095504Notes

Reaction equation

HRID 2095504 reaction equation
[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]

Participants

3

Reactant 1

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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)

Workup

  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

Sources & evidence

ORD record
ord-ef0d0dd8bbd24c10ba1745df8beb7670
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

Loading…