Triethylsilane → 2-(3-Bromo-phenyl)-8-fluoro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-7-carboxylic acid methyl ester

HRID 2045467Notes

Reaction equation

HRID 2045467 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:14]([F:15])=[C:13]2[C:8]([CH:9](O)[C:10]([CH3:24])([CH3:23])[CH:11]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([Br:22])[CH:17]=3)[NH:12]2)=[CH:7][CH:6]=1)=[O:4].C([SiH](CC)CC)C>FC(F)(F)C(O)=O>[CH3:1][O:2][C:3]([C:5]1[C:14]([F:15])=[C:13]2[C:8]([CH2:9][C:10]([CH3:24])([CH3:23])[CH:11]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([Br:22])[CH:17]=3)[NH:12]2)=[CH:7][CH:6]=1)=[O:4]

Participants

4

Reactant 2

HCID 12052TriethylsilaneHCID 674421992-(3-Bromo-phenyl)-8-fluoro-4-hydroxy-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-7-carboxylic acid methyl ester

Product 1

HCID 674422682-(3-Bromo-phenyl)-8-fluoro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-7-carboxylic acid methyl esterYield 50%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
25 °C

Procedure

To a stirred mixture solution of 2-(3-bromo-phenyl)-8-fluoro-4-hydroxy-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-7-carboxylic acid methyl ester (63.0 g, 154 mmol) and triethylsilane (60 mL) at 25° C. was added trifluoroacetic acid (30 mL) dropwise. The resulting mixture solution was stirred at 25° C. for 3 hours. Then the reaction mixture was concentrated in vacuo and the residue was extracted with ethyl acetate (2×200 mL), washed with saturated aqueous sodium bicarbonate solution (4×100 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was triturated with methanol. The resulting precipitate was collected, dried in vacuo to afford 2-(3-bromo-phenyl)-8-fluoro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-7-carboxylic acid methyl ester (30.2 g, 50%) as a yellow oil: LC/MS m/e calcd for C19H19BrFNO2 (M+H)+: 393.27, observed: 392.0 & 394.0. A mixture of 2-(3-bromo-phenyl)-8-fluoro-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-7-carboxylic acid methyl ester (6.0 g, 15.3 mmol), morpholine (13.3 mL, 153 mmol), copper(I) iodide (874 mg, 4.6 mmol), N,N-dimethylglycine hydrochloride (1.3 g, 9.2 mmol) and potassium carbonate (8.5 g, 61.2 mmol) in dimethyl sulfoxide (15 mL) was stirred at 120° C. for 16 h. Then the reaction mixture cooled to room temperature. The reaction mixture was extracted with ethyl acetate (2×150 mL), washed with water (2×50 mL) and saturated aqueous ammonium chloride solution (2×50 mL), dried over anhydrous sodium sulfate and then concentrated in vacuo to afford 8-fluoro-3,3-dimethyl-2-(3-morpholin-4-yl-phenyl)-1,2,3,4-tetrahydro-quinoline-7-carboxylic acid methyl ester (4.8 g, 80%) as a white solid which was used for next step without further purification: LC/MS m/e calcd for C23H27FN2O3 (M+H)+: 399.48, observed: 399.1.

Workup

  1. concentrationThen the reaction mixture was concentrated in vacuo
  2. extractionthe residue was extracted with ethyl acetate (2×200 mL)
  3. washwashed with saturated aqueous sodium bicarbonate solution (4×100 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was triturated with methanol
  7. customThe resulting precipitate was collected
  8. customdried in vacuo

Sources & evidence

ORD record
ord-a05764b5b4ad4090a9c6bfd96d6f0bba
Source dataset
uspto-grants-2013_11
Patent number
US08586747B2

Reaction notes

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