4-(4-Morpholinyl)benzeneacetic acid synthesis

Yield: 90%

Reaction Conditions:

Stage #1:ethyl 4-(morpholin-4-yl)phenylacetate with methanol;lithium hydroxide;water at 20; for 3 h;
Stage #2: with hydrogenchloride;water

Steps:

29
To a solution of ethyl 4-(morphin-4- yl)phenylacetate_(450.0 mg, 1.805 mmol) in Methanol (5.0 ml) was added drop wise 1.0 N LiOH water solution (2.707 ml, 2.707 mmol). The resulting mixture was stirred at room temperature for 3h. The solvent was evaporated under reduced pressure. The residue was suspended into CH₂Cl₂ (20.0 ml). To the suspension was added drop wise cone. HCl until most of the white solid was dissolved. The solution was dried over anhydrous Na₂SO₄, filtered. The filtrate was concentrated. Dried under vacuum to afford the title compound 4-(Morphin-4-yl)phenylacetic acid_as a white solid (360.0 mg, 90%). ¹H NMR (CD₃OD, 400 MHz) δ 7.61 (d, J= 8.61 Hz, 2H); 7.517 (d, J= 8.60 Hz, 2H); 4.140 (t, J= 4.67 Hz, 4H); 3.713 (s, 2H); 3.699 (t, J= 19.60 Hz, 4H); MS (Electrospray): m/z 222.1 (M+H).

References:

MERCK & CO., INC. WO2007/120729, 2007, A2 Location in patent:Page/Page column 65