تفاعل #46133

معادلة التفاعل

NaOH

(S)-2-phenyl-propionic acid 2,2,2-trifluoro-1-[(S)-3-hydroxy-1-((S)-2-phenyl-propionyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-7-yl]-1-trifluoromethyl-ethyl ester

101A

(S)-2-phenyl-propionic acid 2,2,2-trifluoro-1-[(S)-3-(3-methoxycarbonylmethyl-phenoxy)-1-((S)-2-phenyl-propionyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-7-yl]-1-trifluoromethyl-ethyl ester

→

(S)-1-[(S)-3-Hydroxy-7-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3,4,5-tetrahydro-1-benzazepin-1-yl]-2-phenyl-propan-1-one

المذيبات

MeOH

ظروف التفاعل

المعالجة

1. 1
   أخرىThe solvent was removed in vacuo
2. 2
   workup.DISSOLUTIONthe residue was dissolved in THF and neutralized with 1N HCl
3. 3
   أخرىVolatiles were removed under vacuum
4. 4
   أخرىthe product was purified by prep-HPLC
5. 5
   workup.ADDITIONThe fraction containing the title compound
6. 6
   أخرىevaporated
7. 7
   workup.DISSOLUTIONThe residue was dissolved in EtOAc
8. 8
   غسيلwashed with water
9. 9
   تجفيفdried over anhydrous Na2SO4
10. 10
    أخرىThe solvent was removed under vacuum
11. 11
    أخرىto give Example 126

الإجراء التجريبي

To a solution of (S)-2-phenyl-propionic acid 2,2,2-trifluoro-1-[(S)-3-hydroxy-1-((S)-2-phenyl-propionyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-7-yl]-1-trifluoromethyl-ethyl ester (15.0 mg, 0.025 mmol), which was prepared from Example 81 by a similar procedure as that used to prepare 101A, in MeOH (0.5 mL) was added 1N NaOH (0.05 mL, 0.05 mmol) and the mixture was stirred at rt for 5 h. The solvent was removed in vacuo and the residue was dissolved in THF and neutralized with 1N HCl. Volatiles were removed under vacuum and the product was purified by prep-HPLC. The fraction containing the title compound was neutralized with 1N NaOH and evaporated. The residue was dissolved in EtOAc, washed with water, and dried over anhydrous Na2SO4. The solvent was removed under vacuum to give Example 126. LC/MS m/z 462.2 (M+H)+. 1H NMR (500 MHz, Methanol) δ 7.74 (d, 1H), 7.49 (d, 1H), 7.38 (s, 1H), 7.10 (m, 1H), 7.03 (m, 2H), 6.55 (d, 2H), 4.70 (dd, 1H), 3.91 (m, 1H), 3.59 (m, 1H), 2.36 (t, 1H), 2.07 (m, 1H), 1.89 (m, 1H), 1.35 (d, 3H), 1.31 (m, 1H), 1.12 (m, 1H).

المصدر