Acetic Acid → cis-4-(3,5-Bis-trifluoromethyl-benzylamino)-6-hydroxy-7-methoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester

HRID 370051Notes

Reaction equation

HRID 370051 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([OH:18])=[C:13]([O:16][CH3:17])[CH:14]=2)[C@H:9]([NH2:19])[CH2:8][C@@H:7]1[CH3:20])=[O:5])[CH3:2].[F:21][C:22]([F:36])([F:35])[C:23]1[CH:24]=[C:25]([CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=1)[CH:26]=O.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[K+].[K+]>ClCCl.O>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([OH:18])=[C:13]([O:16][CH3:17])[CH:14]=2)[C@H:9]([NH:19][CH2:26][C:25]2[CH:28]=[C:29]([C:31]([F:33])([F:34])[F:32])[CH:30]=[C:23]([C:22]([F:21])([F:35])[F:36])[CH:24]=2)[CH2:8][C@@H:7]1[CH3:20])=[O:5])[CH3:2]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 1362473,5-Bis(trifluoromethyl)benzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 69832492cis-4-Amino-6-hydroxy-7-methoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester

Product 1

HCID 86755994cis-4-(3,5-Bis-trifluoromethyl-benzylamino)-6-hydroxy-7-methoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl esterYield 65.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of cis-4-amino-6-hydroxy-7-methoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (387 mg, 1.38 mmol) in dichloromethane (9 mL) was added 3,5-bis(trifluoromethyl)benzaldehyde (225 μL, 1.38 mmol), followed by acetic acid (80 μL, 1.4 mmol). The reaction was stirred at room temperature for 1 h, then sodium triacetoxyborohydride (440 mg, 2.08 mmol) was added. The reaction was stirred at room temperature for 5 h. Water (5 mL) was added, and the mixture was slowly basified to pH 10 with solid potassium carbonate. The mixture was then extracted with ethyl acetate (3×10 mL), the combined organic phases were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo to give 680 mg crude product. Purification by silica gel chromatography using 0-25% ethyl acetate/hexanes as eluent afforded 458 mg of the title compound (65%).

Workup

  1. stirringThe reaction was stirred at room temperature for 5 h
  2. extractionThe mixture was then extracted with ethyl acetate (3×10 mL)
  3. washthe combined organic phases were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give 680 mg crude product
  8. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-1c72707655d44997bcafe1e64dd19c85
Source dataset
uspto-grants-2000_10
Patent number
US06140342

Reaction notes

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