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

HRID 2296923Notes

Reaction equation

HRID 2296923 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]([NH:20][CH2:21][C:22]2[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[C:24]([C:32]([F:35])([F:34])[F:33])[CH:23]=2)[CH2:8][C@@H:7]1[CH2:36][CH3:37])=[O:5])[CH3:2].[C:38](OC(=O)C)(=[O:40])C.C([O-])=O.[Na+]>C(O)=O.O>[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]([N:20]([CH2:21][C:22]2[CH:27]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:25]=[C:24]([C:32]([F:35])([F:33])[F:34])[CH:23]=2)[CH:38]=[O:40])[CH2:8][C@@H:7]1[CH2:36][CH3:37])=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 2723810Sodium FormateHCID 86584715cis-4-(3,5-bis-trifluoromethyl-benzylamino)-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester

Product 1

HCID 86755977cis-4-[(3,5-Bis-trifluoromethyl-benzyl)-formyl-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl esterYield 86.4%

Reagents, catalysts & solvents 2

HCID 284Formic AcidSolventHCID 962WaterSolvent

Procedure

A solution of cis-4-(3,5-bis-trifluoromethyl-benzylamino)-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester (Example 3E) (2.0 g, 3.65 mmol) in 20 mL of formic acid was treated with acetic anhydride (11.29 g, 111 mmol) and sodium formate (1.25 g, 18.5 mmol). After stirring for 24 h at room temperature, the reaction mixture was diluted with water and extracted with ethyl acetate. 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 10-15% ethyl acetate/hexanes as eluent to afford 1.8 g of the title product. MS m/z 571.2 (M++1); 1H NMR (˜5:1 mixture of formamide rotamers, CDCl3) δ 0.75 (t, 3H), 1.28 (t, 3H), 1.42 (m, 1H), 1.6-1.75 (M, 2H), 2.3 (bm, 1H), 4.15-4.3 (m, 2H), 4.3-4.4 (m, 1H), 4.5-4.7 (bm, 1H), 4.8-5.8 (bm, 2H), 7.14 and 7.08 (s, 1H), 7.5-7.6 (m, 2H), 7.74 (s, 2H), 7.80 and 7.86 (s, 1H), 8.47 and 8.62 (s, 1H).

Workup

  1. extractionextracted with ethyl acetate
  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-22a449542c0141f48a620e3cdfde02ca
Source dataset
uspto-grants-2002_12
Patent number
US06489478B1

Reaction notes

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