Pyridine → N-(3,5-Bis-trifluoromethyl-benzyl)-N-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-acetamide

HRID 2075063Notes

Reaction equation

HRID 2075063 reaction equation
[CH:1]1([CH:7]([O:35][CH3:36])[C:8]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][C:9]=2[CH2:10][NH:11][CH2:12][C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[C:15]([C:23]([F:26])([F:25])[F:24])[CH:14]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1C=CC=CC=1.[C:43](Cl)(=[O:45])[CH3:44]>ClCCl>[F:24][C:23]([F:26])([F:25])[C:15]1[CH:14]=[C:13]([CH:18]=[C:17]([C:19]([F:20])([F:21])[F:22])[CH:16]=1)[CH2:12][N:11]([CH2:10][C:9]1[CH:27]=[C:28]([C:31]([F:32])([F:33])[F:34])[CH:29]=[CH:30][C:8]=1[CH:7]([CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1)[O:35][CH3:36])[C:43](=[O:45])[CH3:44]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6367Acetyl chlorideHCID 58968615N-(2-(cyclohexyl(methoxy)methyl)-5-(trifluoromethyl)benzyl)(3,5-bis(trifluoromethyl)phenyl)methanamine

Product 1

HCID 58968634N-(3,5-Bis-trifluoromethyl-benzyl)-N-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-acetamideYield 37%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution (3,5-bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-amine (Example 41, STEP E, 20 mg, 0.038 mmol) in dichloromethane (1 ml) was added pyridine (9.0 mg, 0.114 mmol) followed by acetyl chloride (2.98 mg, 0.038 mmol) at room temperature and stirred for overnight. Reaction mixture was diluted with dichloromethane and washed with water. The organic layer was dried over anhydrous magnesium sulphate and concentrated in vacuo. The product was purified on Biotage column (12+S), eluting with 2% ethyl acetate in heptane (1 CV), 2-20% (10CV), 20% (2CV) to yield the title compound (8 mg, 37%) as colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 0.9 (m, 6H) 1.2 (m, 3H) 1.7 (m, 1H) 1.9 (m, 1H) 2.2 (s, 3H) 3.1 (s, 3H) 3.9 (m, 1H) 4.6 (m, 4H) 7.4 (m, 1H) 7.5 (m, 2H) 7.6 (m, 2H) 7.8 (s, 1H). MS (ES+) Calc: 569.2, Found: 614.2 (M+45).

Workup

  1. customReaction mixture
  2. washwashed with water
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulphate
  4. concentrationconcentrated in vacuo
  5. customThe product was purified on Biotage column (12+S)
  6. washeluting with 2% ethyl acetate in heptane (1 CV), 2-20% (10CV), 20% (2CV)

Sources & evidence

ORD record
ord-78124b35d7fe4bdfbb59ded15cd65c96
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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