Potassium Carbonate → Methyl (3-{3-[[2-Chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino]propoxy}-phenyl)acetate

HRID 902686Notes

Reaction equation

HRID 902686 reaction equation
Br[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[CH:9]=[CH:10][CH:11]=1.[Cl:17][C:18]1[C:39]([C:40]([F:43])([F:42])[F:41])=[CH:38][CH:37]=[CH:36][C:19]=1[CH2:20][NH:21][CH2:22][CH:23]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Cl:17][C:18]1[C:39]([C:40]([F:41])([F:42])[F:43])=[CH:38][CH:37]=[CH:36][C:19]=1[CH2:20][N:21]([CH2:22][CH:23]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[CH:9]=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 10565189Methyl [3-(3-bromopropoxy)phenyl]acetateHCID 58913799(2-Chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amine

Product 1

HCID 10188816Methyl (3-{3-[[2-Chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino]propoxy}-phenyl)acetateYield 81.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of methyl [3-(3-bromopropoxy)phenyl]acetate (1.0 g, 3.48 mmole) and N-[2-chloro-3-(trifluoromethyl)benzyl]-2,2-diphenylethanamine (1.63 g, 4.18 mmole) in 20 mL of acetonitrile was treated with potassium carbonate (0.72 g, 5.2 mmol). The reaction mixture was heated to reflux and stirred for 4 days. The reaction mixture was filtered, and the filtrate was concentrated in vacuo. The crude product was purified by flash chromatography (silica gel cartridge, Biotage 32-63 um, 60A) with 10% EtOAc:hexanes as the eluent to afford 1.69 g (81% yield) of the title compound as a viscous oil: 1H NMR (CDCl3, 400 MHz) δ 7.46-7.44 (d, 1 H, J=7.7), 7.25-7.14 (m, 12 H), 6.91-6.84 (m, 2 H), 6.66-6.62 (m, 2 H), 4.15-4.09 (t, 1 H. J=7.6), 3.78 (s, 1 H), 3.69-3.66 (m, 5 H), 3.59(S, 2 H), 3.15-3.13 (d, 2 H, J=7.7), 2.72-2.68 (t, 2 H, J=6.6), 1.87-1.80 (m, 2 H); MS (ESP+) m/e 597 (MH+); TLC (hexanes:EtOAc/9:1) Rf=0.36.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. filtrationThe reaction mixture was filtered
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe crude product was purified by flash chromatography (silica gel cartridge, Biotage 32-63 um, 60A) with 10% EtOAc

Sources & evidence

ORD record
ord-223ba84e842e4b14ae035014e2a8a5ec
Source dataset
uspto-grants-2008_04
Patent number
US07365085B2

Reaction notes

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