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

HRID 2184076노트

반응식

HRID 2184076 반응식
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]

참가 물질

6

반응물 4

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

생성물 2

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

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-9e6b6c00050a429288d7e4ea43ea6de0
출처 데이터셋
uspto-grants-2005_05
특허 번호
US06900244B2

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