Sodium Hydroxide → (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

HRID 17855Notes

Reaction equation

HRID 17855 reaction equation
[F:1][C:2]([F:42])([F:41])[C:3]([O:30]C(=O)[C@H](C1C=CC=CC=1)C)([C:8]1[CH:9]=[CH:10][C:11]2[N:17]([C:18](=[O:27])[C@H:19]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH3:20])[CH2:16][C@@H:15]([OH:28])[CH2:14][CH2:13][C:12]=2[CH:29]=1)[C:4]([F:7])([F:6])[F:5].FC(F)(F)C(OC(=O)[C@H](C1C=CC=CC=1)C)(C1C=CC2N(C(=O)[C@H](C3C=CC=CC=3)C)C[C@@H](OC3C=CC=C(CC(OC)=O)C=3)CCC=2C=1)C(F)(F)F.[OH-].[Na+]>CO>[OH:28][C@H:15]1[CH2:14][CH2:13][C:12]2[CH:29]=[C:8]([C:3]([OH:30])([C:2]([F:1])([F:41])[F:42])[C:4]([F:7])([F:5])[F:6])[CH:9]=[CH:10][C:11]=2[N:17]([C:18](=[O:27])[C@H:19]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH3:20])[CH2:16]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 86612111(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 esterHCID 86612112HCID 86612112, compound

Product 1

HCID 16660896(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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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).

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in THF and neutralized with 1N HCl
  3. customVolatiles were removed under vacuum
  4. customthe product was purified by prep-HPLC
  5. additionThe fraction containing the title compound
  6. customevaporated
  7. dissolutionThe residue was dissolved in EtOAc
  8. washwashed with water
  9. dry with materialdried over anhydrous Na2SO4
  10. customThe solvent was removed under vacuum
  11. customto give Example 126

Sources & evidence

ORD record
ord-78e7680319ce4f77916ddc0d86a4e158
Source dataset
uspto-grants-2010_06
Patent number
US07741317B2

Reaction notes

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