(4S,7S)-4-(3-Bromo-5-ethoxy-4-hydroxy-phenyl)-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carboxylic acid [1-(4-methoxy-phenyl)ethyl]-amide → (4R,7S)-4-(3-Bromo-5-ethoxy-4-hydroxy-phenyl)-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile

HRID 910764Notes

Reaction equation

HRID 910764 reaction equation
COC1C=CC(C([NH:11][C:12]([C:14]2[C@@H:23]([C:24]3[CH:29]=[C:28]([O:30][CH2:31][CH3:32])[C:27]([OH:33])=[C:26]([Br:34])[CH:25]=3)[C:22]3[C:21](=[O:35])[CH2:20][C@@H:19]([CH2:36][CH2:37][CH3:38])[CH2:18][C:17]=3[NH:16][C:15]=2[CH3:39])=O)C)=CC=1>C(O)(C(F)(F)F)=O>[Br:34][C:26]1[CH:25]=[C:24]([C@H:23]2[C:22]3[C:21](=[O:35])[CH2:20][C@@H:19]([CH2:36][CH2:37][CH3:38])[CH2:18][C:17]=3[NH:16][C:15]([CH3:39])=[C:14]2[C:12]#[N:11])[CH:29]=[C:28]([O:30][CH2:31][CH3:32])[C:27]=1[OH:33]

Participants

3

Reactant 1

HCID 67418207(4S,7S)-4-(3-Bromo-5-ethoxy-4-hydroxy-phenyl)-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carboxylic acid [1-(4-methoxy-phenyl)ethyl]-amide

Product 1

HCID 67417503(4R,7S)-4-(3-Bromo-5-ethoxy-4-hydroxy-phenyl)-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
75 °C

Procedure

A solution of (4S,7S)-4-(3-Bromo-5-ethoxy-4-hydroxy-phenyl)-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinoline-3-carboxylic acid [1-(4-methoxy-phenyl)ethyl]-amide (Example 72d, 1.43 g) was dissolved in TFA (30 mL) and stirred at 75° C. for 1 hr. The TFA was evaporated in vacuo and the residue was then dissolved in dichloromethane (30 ml). Triethylamine (1.04 g) and trifluoroacetic acid anhydride (0.95 g) were added dropwise at 0° C. for 15 minutes. The reaction was stirred for 1 hr and the reaction mixture was washed with water (20 ml). The organic layer was dried (MgSO4), filtered, concentrated in vacuo and concentrated. The residue was purified by chromatography on silicagel in heptane/ethyl acetate 1/0->0/1 (v/v) as eluent.

Workup

  1. customThe TFA was evaporated in vacuo
  2. dissolutionthe residue was then dissolved in dichloromethane (30 ml)
  3. additionTriethylamine (1.04 g) and trifluoroacetic acid anhydride (0.95 g) were added dropwise at 0° C. for 15 minutes
  4. stirringThe reaction was stirred for 1 hr
  5. washthe reaction mixture was washed with water (20 ml)
  6. dry with materialThe organic layer was dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography on silicagel in heptane/ethyl acetate 1/0->0/1 (v/v) as eluent

Sources & evidence

ORD record
ord-2434d039a48f44dca8d4286666e077d9
Source dataset
uspto-grants-2011_09
Patent number
US08022218B2

Reaction notes

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