Diisopropylethylamine → Tert-butyl 4-(3-(3,5-dimethoxybenzylamino)-4-(2,2,2-trifluoroacetyl)-phenyl)piperazine-1-carboxylate

HRID 2426000Notes

Reaction equation

HRID 2426000 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:21]=[C:22]([O:24][CH3:25])[CH:23]=1)[CH2:6][NH:7][C:8]1[CH:13]=[C:12](F)[CH:11]=[CH:10][C:9]=1[C:15](=[O:20])[C:16]([F:19])([F:18])[F:17].[C:26]([N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].C(N(CC)C(C)C)(C)C>C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:21]=[C:22]([O:24][CH3:25])[CH:23]=1)[CH2:6][NH:7][C:8]1[CH:13]=[C:12]([N:36]2[CH2:35][CH2:34][N:33]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:38][CH2:37]2)[CH:11]=[CH:10][C:9]=1[C:15](=[O:20])[C:16]([F:19])([F:18])[F:17]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 587072721-(2-(3,5-Dimethoxybenzylamino)-4-fluorophenyl)-2,2,2-trifluoroethanone

Product 1

HCID 58707343Tert-butyl 4-(3-(3,5-dimethoxybenzylamino)-4-(2,2,2-trifluoroacetyl)-phenyl)piperazine-1-carboxylateYield 135.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 1-(2-(3,5-dimethoxybenzylamino)-4-fluorophenyl)-2,2,2-trifluoroethanone (527 mg, 1.47 mmol), N-Boc-piperazine (296 mg, 1.62 mmol) and N,N-diisopropylethylamine (0.51 mL, 2.94 mmol) in acetonitrile was stirred at reflux for 48 h. The reaction mixture was cooled down and concentrated under reduced pressure. The residue was taken up in dichloromethane, washed with water, dried and concentrated in vacuo to yield 1.04 g of the crude aniline. The crude product was purified by PTLC (20% ethyl acetate in hexanes) to yield 230 mg (30%) of tert-butyl 4-(3-(3,5-dimethoxybenzylamino)-4-(2,2,2-trifluoroacetyl)phenyl)piperazine-1-carboxylate: 1H NMR (400 MHz, CD3OD): δ 9.32 (br t, 1H), 7.63 (dd, 1H), 6.50 (d, 2H), 6.37 (t, 1H), 6.19 (dd, 1H), 5.81 (d, 1H), 4.39 (d, 2H), 3.77 (s, 6H), 3.52-3.49 (m, 4H), 3.35-3.32 (m, 4H), 1.48 (s, 9H). MS (ESI) m/z: Calculated: 523.23; Observed: 546.3 (M++23).

Workup

  1. temperatureat reflux for 48 h
  2. temperatureThe reaction mixture was cooled down
  3. concentrationconcentrated under reduced pressure
  4. washwashed with water
  5. customdried
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-539c0665778d4221aa9db6b291bbc9fd
Source dataset
uspto-grants-2011_06
Patent number
US07968538B2

Reaction notes

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