Diisopropylethylamine → t-Butyl 4-(3-(3,5-dichlorobenzylamino)-4-(2,2,2-trifluoroacetyl)phenyl)piperazine-1-carboxylate

HRID 1910565Notes

Reaction equation

HRID 1910565 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[C:21]([Cl:23])[CH:22]=1)[CH2:5][NH:6][C:7]1[CH:12]=[C:11](F)[CH:10]=[CH:9][C:8]=1[C:14](=[O:19])[C:15]([F:18])([F:17])[F:16].[N:24]1([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]1.C(N(CC)C(C)C)(C)C>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[C:21]([Cl:23])[CH:22]=1)[CH2:5][NH:6][C:7]1[CH:12]=[C:11]([N:27]2[CH2:26][CH2:25][N:24]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:29][CH2:28]2)[CH:10]=[CH:9][C:8]=1[C:14](=[O:19])[C:15]([F:18])([F:17])[F:16]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 587073441-(2-(3,5-Dichlorobenzylamino)-4-fluorophenyl)-2,2,2-trifluoroethanone

Product 1

HCID 58707280t-Butyl 4-(3-(3,5-dichlorobenzylamino)-4-(2,2,2-trifluoroacetyl)phenyl)piperazine-1-carboxylateYield 28%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 1-(2-(3,5-dichlorobenzylamino)-4-fluorophenyl)-2,2,2-trifluoroethanone (0.78 g, 2.1 mmol), t-butyl piperazine-1-carboxylate (0.41 g, 2.2 mmol), N,N-diisopropylethylamine (0.8 mL, 4.4 mmol) and acetonitrile (10 mL) was heated at reflux for 18 h, cooled to room temperature and concentrated in vacuo. The residue was dissolved in ethyl acetate; this solution was washed with water, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel using 10% ethyl acetate in hexanes as eluent to yield the title compounds as a yellow solid (0.31 g, 28%). 1H NMR (400 MHz, CDCl3): δ 9.38 (br, 1 H), 7.67 (d, 1 H), 7.31 (s, 1 H), 7.21 (s, 2 H), 6.13 (dd, 1 H), 5.70 (d, 1 H), 4.42 (d, 2 H), 3.54 (m, 4 H), 3.38 (m, 4 H), 1.49 (s, 9 H). MS (ESI) m/z: Calculated: 531; Observed: 532 (M+H+).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 18 h
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washthis solution was washed with water
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel using 10% ethyl acetate in hexanes as eluent

Sources & evidence

ORD record
ord-b382b114e1ec47a8b98f22af0db91c62
Source dataset
uspto-grants-2013_12
Patent number
US08604021B2

Reaction notes

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