Acetic Acid → cis-4-[(3,5-Bis-trifluoromethyl-benzyl)-amino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester

HRID 279366Notes

Reaction equation

HRID 279366 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH3:19])=[C:13]([O:16][CH3:17])[CH:14]=2)[C@H:9]([NH2:20])[CH2:8][C@@H:7]1[CH3:21])=[O:5])[CH3:2].C(O)(=O)C.[F:26][C:27]([F:41])([F:40])[C:28]1[CH:29]=[C:30]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[CH:31]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[K+].[K+]>ClC(Cl)C.O>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([O:18][CH3:19])=[C:13]([O:16][CH3:17])[CH:14]=2)[C@H:9]([NH:20][CH2:31][C:30]2[CH:33]=[C:34]([C:36]([F:38])([F:39])[F:37])[CH:35]=[C:28]([C:27]([F:26])([F:40])[F:41])[CH:29]=2)[CH2:8][C@@H:7]1[CH3:21])=[O:5])[CH3:2]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 11430Potassium CarbonateHCID 1362473,5-Bis(trifluoromethyl)benzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 69832909cis-4-amino-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester

Product 1

HCID 86755983cis-4-[(3,5-Bis-trifluoromethyl-benzyl)-amino]-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl esterYield 70.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 63651,1-DichloroethaneSolvent

Procedure

A solution of cis-4-amino-6,7-dimethoxy-2-methyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (527 mg, 1.8 mmol) in dichloroethane (12 mL) was treated sequentially with acetic acid (0.1 mL, 1.8 mmol) and 3,5-bis-trifluoromethyl-benzaldehyde (0.30 mL, 1.8 mmol). After stirring 35 minutes at room temperature, sodium triacetoxyborohydride (570 mg, 2.7 mmol) was added to the mixture. After 3 days, 20 mL of water was added and the mixture made basic (pH 10) with potassium carbonate. The mixture was extracted with ethyl acetate (3×35 mL), the combined organic layers were washed with brine (20 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with 0-20% ethyl acetate in hexanes to provide the title compound (663 mg). 1H NMR (CDCl3) δ1.22 (d, 3H), 1.3 (t, 3H), 1.5 (m, 1H), 2.6 (m, 1H), 3.55 (dd, 1H), 3.87 (s, 3H), 3.89 (s, 3H), 4.1-4.6 (m, 5H), 7.06 (s, 1H), 7.08 (s, 1H), 7.8 (s, 1H), 7.95 (s, 2H).

Workup

  1. waitAfter 3 days
  2. extractionThe mixture was extracted with ethyl acetate (3×35 mL)
  3. washthe combined organic layers were washed with brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 0-20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-dd4a8541310f493b92aae20946c5d01e
Source dataset
uspto-grants-2002_03
Patent number
US06362198B1

Reaction notes

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