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

HRID 881662Notes

Reaction equation

HRID 881662 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.[Cl:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][CH:39]=1)[CH2:35]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)[CH2:35][C:34]2[CH:37]=[CH:38][CH:39]=[C:32]([Cl:31])[CH:33]=2)[CH:6]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 698381-(Bromomethyl)-3-chlorobenzeneHCID 68906807{3-[3-(2,2-Diphenyl-ethylamino)-propoxy]-phenyl}-acetic acid methyl ester

Product 1

HCID 68906861(3-{3-[(2,2-Diphenyl-ethyl)-(3-chloro-benzyl)-amino]-propoxy}-phenyl)-acetic acid methyl esterYield 78.1%

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) (0.34 g, 0.0008 mol) in DMF (10 mL), was added 3-chlorobenzyl bromide (0.25 g, 0.0012 mol) and powdered potassium carbonate (0.77 g, 0.0056 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 (3×20 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 0.33 g in 77% yield. 1H NMR (CDCl3) δ 7.23 (d, 2H), 7.18 (m, 4H), 7.14 (m, 6H), 6.91 (d, 2H), 6.83 (d, 1H), 6.82 (d, 1H), 6.65 (s, 1H), 6.63 (d, 1H), 4.16 (t, 1H), 3.67 (s, 3H), 3.63 (t, 2H), 3.57 (s, 2H), 3.55 (s, 2H), 3.05 (d, 2H), 2.63 (t, 2H), 1.80 (t, 2H); 13C NMR (CDCl3) δ 173.3, 160.5, 144.7, 143.3, 136.6, 135.3, 130.8, 130.7, 130.3, 129.7, 129.6, 128.4, 128.3, 127.7, 122.7, 116.9, 114.5, 66.9, 61.1, 60.1, 53.5, 51.8, 51.1, 42.7, 28.2.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureAfter cooling
  3. extractionextracted with EtOAc (3×20 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-d6dc372457a0444e896079803efb65ff
Source dataset
uspto-grants-2015_03
Patent number
US08993628B2

Reaction notes

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