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 370035Notes

Reaction equation

HRID 370035 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) δ 1.22 (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-15e9d9219e194595851028b6d3cf6d5c
Source dataset
uspto-grants-2000_10
Patent number
US06140342

Reaction notes

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