Potassium Carbonate → (3-{3-[(2,2-Diphenyl-ethyl)-(3-trifluoromethyl-benzyl)-amino]-propoxy}-phenyl)-acetic acid methyl ester

HRID 881661Notes

Reaction equation

HRID 881661 reaction equation
[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][NH:15][CH2:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:6]=1.[F:31][C:32]([F:42])([F:41])[C:33]1[CH:34]=[C:35]([CH:38]=[CH:39][CH:40]=1)[CH2:36]Br.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:36][C:35]2[CH:38]=[CH:39][CH:40]=[C:33]([C:32]([F:31])([F:41])[F:42])[CH:34]=2)[CH:6]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 1230611-(Bromomethyl)-3-(trifluoromethyl)benzeneHCID 68906807{3-[3-(2,2-Diphenyl-ethylamino)-propoxy]-phenyl}-acetic acid methyl ester

Product 1

HCID 68910010(3-{3-[(2,2-Diphenyl-ethyl)-(3-trifluoromethyl-benzyl)-amino]-propoxy}-phenyl)-acetic acid methyl esterYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of {3-[3-(2,2-diphenyl-ethylamino)-propoxy]-phenyl}-acetic acid methyl ester (3) (0.40 g, 0.001 mol) in DMF (10 mL), was added 3-trifluoromethylbenzyl bromide (0.24 g, 0.001 mol) and powdered potassium carbonate (0.96 g, 0.007 mol), the reaction mixture was heated and stirred at 45° C. for 18 hours. After cooling, the reaction mixture was diluted with water (30 mL) and extracted with EtOAc (3×25 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4, concentrated to an oil, which was purified by flash chromatography (8:2 Hexanes/EtOAc) to give the desired product as oil 0.43 g in 77% yield. 1H NMR (CDCl3) δ 7.40 (d, 1H), 7.37 (s, 1H), 7.24 (m, 7H), 7.19 (m, 6H), 6.83 (d, 1H), 6.62 (s, 1H), 6.59 (dd, 1H), 4.16 (t, 1H), 3.67 (s, 3H), 3.63 (s, 2H), 3.58 (t, 2H), 3.55 (s, 2H), 3.08 (d, 2H), 2.61 (t, 2H), 1.79 (t, 2H); 13C NMR (CDCl3) δ 173.4, 160.4, 144.7, 143.7, 142.2, 136.6, 133.8, 133.5, 131.9, 130.8, 130.2, 129.9, 129.8, 127.8, 126.8, 125.1, 125.0, 122.7, 116.8, 115.7, 114.5, 66.8, 61.1, 60.2, 53.5, 51.8, 42.6, 28.2.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureAfter cooling
  3. extractionextracted with EtOAc (3×25 mL)
  4. washThe combined organic extracts were washed with brine (15 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated to an oil, which
  7. customwas purified by flash chromatography (8:2 Hexanes/EtOAc)

Sources & evidence

ORD record
ord-640570ba1800457587798b719f734dfb
Source dataset
uspto-grants-2015_03
Patent number
US08993628B2

Reaction notes

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