p-Anisoyl chloride → HCID 11588348, compound

HRID 731997Notes

Reaction equation

HRID 731997 reaction equation
F[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[CH:16]([NH2:18])[CH3:17].C[O:20][C:21]1[CH:29]=[CH:28][C:24]([C:25](Cl)=[O:26])=[CH:23][CH:22]=1.C(N(CC)C(C)C)(C)C>ClCCl>[F:8][C:6]1[CH:7]=[CH:2][C:3]2[C:9]3[C:10]([CH:16]([CH3:17])[N:18]([C:25]([C:24]4[CH:28]=[CH:29][C:21]([OH:20])=[CH:22][CH:23]=4)=[O:26])[C:4]=2[CH:5]=1)=[CH:11][C:12]([F:15])=[CH:13][CH:14]=3

Participants

5

Reactant 3

HCID 7477p-Anisoyl chlorideHCID 81531DiisopropylethylamineHCID 22482308HCID 22482308, compound

Product 1

HCID 11588348HCID 11588348, compoundYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Methoxy-N-[1-(2′,4,4′-trifluoro-1,1′-biphenyl-2-yl)ethyl]benzamide—A stirred solution of 1-(2′,4,4′-trifluoro-1,1′-biphenyl-2-yl)ethylamine (0.71 g, 2.84 mmol) in dichloromethane (5 mL) was treated with 4-methoxybenzoyl chloride (0.51 g, 3.0 mmol), and N,N-diisopropylethylamine (0.77 g, 6.0 mmol). The reaction was stirred at room temperature for twelve hours, and the solvent evaporated in vacuo to a crude oil. The crude oil was purified by preparative liquid chromatography on a Biotage® 40 Mi column of pre-packed silica gel (90 g), eluting with a gradient of between 5% and 50% methyl tert-butyl ether in hexane at a flow rate of 40 mL/min to afford, after evaporation of the solvent, a colorless oil. Crystallization of the colorless oil from ethyl acetate-hexane yielded the title compound (0.98 g, 2.54 mmol, 90%) as a homogeneous, colorless, crystalline solid, m.p. 163-165° C.; MS [(+ESI), m/z]: 386 [M+H]+; IR (Solid), vmax: 3257, 1620, 1606, 1503, 1329, 1249, 1175, 1032, 844, 777, 670 cm−1; 1H NMR (400 MHz, DMSO-d6) δ: 1.29 (d, J=5.4 Hz, 3H), 3.80 (s, 3H), 4.93 (broad s, 1H), 6.93 (d, J=8.8 Hz, 2H), 7.14 (td, J=8.5, 2.7 Hz, 1H), 7.22 (dd, J=8.5, 5.9 Hz, 2H), 7.37 (t, 2H), 7.46 (d, J=9.1 Hz, 1H), 7.61 (d, J=4.7 Hz, 1H), 7.83 (d, J=7.2 Hz, 2H), 8.66 (d, J=3.9 Hz, 1H), exists as approximate 2:1 mixture of rotamers; Anal. calcd for C22H18F3NO2: C, 68.57; H, 4.71; N, 3.63. Found: C, 68.65; H, 4.80 N, 3.48.

Workup

  1. customthe solvent evaporated in vacuo to a crude oil
  2. customThe crude oil was purified by preparative liquid chromatography on a Biotage® 40 Mi column of pre-packed silica gel (90 g)
  3. washeluting with a gradient of between 5% and 50% methyl tert-butyl ether in hexane at a flow rate of 40 mL/min
  4. customto afford
  5. customafter evaporation of the solvent
  6. customCrystallization of the colorless oil from ethyl acetate-hexane

Sources & evidence

ORD record
ord-7fc7f2b0abbf4c64aba83b7618ead555
Source dataset
uspto-grants-2009_09
Patent number
US07585871B2

Reaction notes

Loading…