反応 #46133

反応方程式

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

溶媒

MeOH

反応条件

後処理

1. 1
   その他The solvent was removed in vacuo
2. 2
   workup.DISSOLUTIONthe residue was dissolved in THF and neutralized with 1N HCl
3. 3
   その他Volatiles were removed under vacuum
4. 4
   その他the product was purified by prep-HPLC
5. 5
   workup.ADDITIONThe fraction containing the title compound
6. 6
   その他evaporated
7. 7
   workup.DISSOLUTIONThe residue was dissolved in EtOAc
8. 8
   洗浄washed with water
9. 9
   乾燥dried over anhydrous Na2SO4
10. 10
    その他The solvent was removed under vacuum
11. 11
    その他to give Example 126

実験手順

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).

出典