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

HRID 881657Notes

Reaction equation

HRID 881657 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:43])([F:42])[O:33][C:34]1[CH:35]=[C:36]([CH:39]=[CH:40][CH:41]=1)[CH2:37]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)[CH2:37][C:36]2[CH:39]=[CH:40][CH:41]=[C:34]([O:33][C:32]([F:31])([F:42])[F:43])[CH:35]=2)[CH:6]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 7371761-(Bromomethyl)-3-(trifluoromethoxy)benzeneHCID 68906807{3-[3-(2,2-Diphenyl-ethylamino)-propoxy]-phenyl}-acetic acid methyl ester

Product 1

HCID 68908942(3-{3-[(2,2-Diphenyl-ethyl)-(3-trifluoromethoxy-benzyl)-amino]-propoxy}-phenyl)-acetic acid methyl esterYield 88%

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) (0.5 g, 0.0012 mol) in DMF (10 mL), was added 3-(trifluoromethoxy)benzyl bromide (0.47 g, 0.0018 mol) and powdered potassium carbonate (1.16 g, 0.0084 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 (9:1 Hexanes/EtOAc) to give the desired product as oil 0.61 g in 88% yield. 1H NMR (CDCl3) δ 7.20 (s, 1H), 7.19 (m, 11H), 7.04 (s, 1H), 7.01 (t, 2H), 6.88 (d, 1H), 6.69 (m 2H), 4.20 (t, 1H), 3.70 (s, 3H), 3.63 (s, 2H), 3.59 (s, 2H), 3.13 (d, 2H), 2.67 (t, 2H), 1.84 (t, 2H); 13C NMR (CDCl3) δ 173.4, 160.5, 149.6, 144.8, 136.7, 131.0, 130.9, 130.0, 129.8, 129.7, 129.6, 128.4, 127.8, 122.8, 122.7, 122.5, 120.6, 116.9, 114.5, 66.8, 61.3, 60.1, 53.4, 51.9, 51.2, 42.7, 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 (9:1 Hexanes/EtOAc)

Sources & evidence

ORD record
ord-2d414372ebe3403a98592a6b49afd5f9
Source dataset
uspto-grants-2015_03
Patent number
US08993628B2

Reaction notes

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