Potassium Carbonate → (3-{3-[(2,2-Diphenyl-ethyl)-(3,5-bis(trifluoromethyl)-benzyl)-amino]-propoxy}-phenyl)-acetic acid methyl ester

HRID 881659Notes

Reaction equation

HRID 881659 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:46])([F:45])[C:33]1[CH:34]=[C:35]([CH:38]=[C:39]([C:41]([F:44])([F:43])[F:42])[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]=[C:39]([C:41]([F:43])([F:44])[F:42])[CH:40]=[C:33]([C:32]([F:31])([F:45])[F:46])[CH:34]=2)[CH:6]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 68906807{3-[3-(2,2-Diphenyl-ethylamino)-propoxy]-phenyl}-acetic acid methyl ester

Product 1

HCID 86626714(3-{3-[(2,2-Diphenyl-ethyl)-(3,5-bis(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) (0.50 g, 0.0012 mol) in DMF (10 mL), was added 3,5-bis (trifluoromethyl)-benzyl bromide (0.50 g, 0.0016 mol) and powdered potassium carbonate (1.55 g, 0.011 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 0.57 g in 77% yield. 1H NMR (CDCl3) δ 7.61 (s, 1H), 7.50 (s, 2H), 7.24 (m, 12H), 6.83 (d, 1H), 6.62 (s, 1H), 6.59 (dd 1H), 4.19 (t, 1H), 3.68 (s, 2H), 3.67 (s, 3H), 3.60 (t, 2H), 3.56 (d, 2H), 3.14 (d, 2H), 2.64 (t, 2H), 1.83 (t, 2H); 13C NMR (CDCl3) δ 173.3, 160.3, 144.3, 136.7, 132.8, 130.9, 130.1, 129.9, 129.7, 129.5, 128.0, 125.9, 123.7, 122.9, 122.3, 116.2, 114.5, 114.4, 66.6, 61.1, 59.7, 53.4, 52.1, 51.3, 42.6, 28.1.

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-d921c1660920475c8502b0b48ca16341
Source dataset
uspto-grants-2015_03
Patent number
US08993628B2

Reaction notes

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