Methanol → Methyl N-{4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl}-phenylalaninate

HRID 2184076Notes

Reaction equation

HRID 2184076 reaction equation
S(=O)(=O)(O)[OH:2].[C:6]1([CH2:12][CH:13]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([C:23]([OH:32])([C:28]([F:31])([F:30])[F:29])[C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=2)[C:14]#N)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[OH-:33].[Na+].[CH3:35][OH:36]>>[OH2:2].[C:23]([OH:32])([C:28]([F:31])([F:30])[F:29])=[O:33].[F:25][C:24]([F:27])([F:26])[C:23]([C:20]1[CH:21]=[CH:22][C:17]([NH:16][C@H:13]([C:14]([O:36][CH3:35])=[O:33])[CH2:12][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)=[CH:18][CH:19]=1)([OH:32])[C:28]([F:31])([F:30])[F:29]

Participants

6

Reactant 4

HCID 887MethanolHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 224756413-Phenyl-2-({4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl}-amino)propanenitrile

Product 2

HCID 22392675Trifluoroacetic acid waterHCID 86592172Methyl N-{4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl}-phenylalaninateYield 50%

Procedure

Sulfuric acid (1 mL) was added to the product of step 1 (1.4 g, 3.65 mmol) and the resulting mixture stirred at ambient temperature for 2.5 h. Methanol (2 mL) was added and the solution heated at reflux for 3 h. The solution was cooled to room temperature and 1 M NaOH added until a pH=8 was reached. The solution was extracted with ethyl acetate and the combined organics washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification by reverse phase HPLC using a gradient elution of 60:40 H2O/TFA:CH3CN to 0:100 H2O/TFA:CH3CN at 254 nm afforded the title compound as a yellow oil (768 mg, 50%). 1H NMR (CDCl3) δ 7.47 (d, 2H), 7.32-7.25 (m, 3H), 7.14 (m, 2H), 6.61 (d, 2H), 4.38 (t, 1H), 3.70 (s, 3H), 3.25 (brs, 1H), 3.17 (dd, 1H), 3.11 (dd, 1H). MS (ES+) m/z422 (MH+). Anal. Calc. for C19H17NO3F6+0.1H2O: C, 53.93; H, 4.10; N, 3.31. Found: C, 53.73; H, 3.92; N, 3.54.

Workup

  1. temperaturethe solution heated
  2. temperatureat reflux for 3 h
  3. temperatureThe solution was cooled to room temperature
  4. extractionThe solution was extracted with ethyl acetate
  5. washthe combined organics washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customPurification by reverse phase HPLC
  9. washa gradient elution of 60:40 H2O/TFA

Sources & evidence

ORD record
ord-9e6b6c00050a429288d7e4ea43ea6de0
Source dataset
uspto-grants-2005_05
Patent number
US06900244B2

Reaction notes

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