Acetic Acid → cis-4-(3,5-bis-trifluoromethyl-benzylamino)-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester

HRID 1530897Notes

Reaction equation

HRID 1530897 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([C:16]([F:19])([F:18])[F:17])=[CH:13][CH:14]=2)[C@H:9]([NH2:20])[CH2:8][C@@H:7]1[CH2:21][CH3:22])=[O:5])[CH3:2].C(O)(=O)C.[F:27][C:28]([F:42])([F:41])[C:29]1[CH:30]=[C:31]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[CH:32]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>[OH-].[K+]>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[CH:11][C:12]([C:16]([F:17])([F:18])[F:19])=[CH:13][CH:14]=2)[C@H:9]([NH:20][CH2:32][C:31]2[CH:34]=[C:35]([C:37]([F:39])([F:40])[F:38])[CH:36]=[C:29]([C:28]([F:27])([F:41])[F:42])[CH:30]=2)[CH2:8][C@@H:7]1[CH2:21][CH3:22])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1362473,5-Bis(trifluoromethyl)benzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 69580533cis-4-Amino-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester

Product 1

HCID 86584715cis-4-(3,5-bis-trifluoromethyl-benzylamino)-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl esterYield 91.5%

Reagents, catalysts & solvents 1

HCID 14797Potassium HydroxideSolvent

Procedure

A solution of cis-4-amino-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (Example 7D) (8.8 g, 27.8 mmol) was treated sequentially with acetic acid (5.0 g, 83.5 mmol), 3,5-bis-trifluoromethyl-benzaldehyde (6.74 g, 27.8 mmol), followed by sodium triacetoxyborohydride (29.5 g, 139.2 mmol). After stirring at room temperature for 24 h, the mixture was combined with 500 mL of 1M potassium hydroxide, and the aqueous layer was extracted with dichloromethane (2×200 mL). The combined organic phases were dried over magnesium sulfate, filtered and concentrated in vacuo to afford the crude product, which was purified by silica gel chromatography using 5-10% ethyl acetate/hexanes as eluent to afford 13.8 g of the title product. 1H NMR (CDCl3) δ 0.85 (t, 3H), 1.27 (m, 4H), 1.45 (m, 2H), 1.67 (m, 1H), 2.66 (m, 1H), 3.56 (m, 1H), 4.1-4.3 (m, 4H), 4.42 (m, 1H), 7.49 (d, 1H, J=8.5 Hz), 7.52 (d,1H, J=8.5 Hz), 7.76 (s, 1H), 7.79 (s, 1H), 7.91 (s, 2H).

Workup

  1. extractionthe aqueous layer was extracted with dichloromethane (2×200 mL)
  2. dry with materialThe combined organic phases were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto afford the crude product, which
  6. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-13ee7a4c9a7d43e4a6dd1501a17e1f51
Source dataset
uspto-grants-2001_03
Patent number
US06197786B1

Reaction notes

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