(S)-2-ETHOXY-3-[4-[2-(4-METHANESULFONYLOXY-PHENYL)-ETHOXY]-PHENYL]-PROPIONIC ACID synthesis

Yield: 79%

Reaction Conditions:

with sulfuric acid;acetic acid in water;ethyl acetate

Steps:

1.g g
g (S)-2-Ethoxy-3-[4-(2-{4-methanesulfonyloxyphenyl}ethoxy)phenyl]propanoic acid (S)-2-Ethoxy-N-(2-hydroxy(R)-1-phenylethyl)-3-[4-(2-{4-methanesulfonyloxyphenyl}ethoxy)phenyl]propanoic amide (4.49 g; 8.59 mmole), concentrated sulfuric acid (12.5 Ml), dioxan (50 ml) and water (50 ml) were stirred at 80° C. for 6 hours. After cooling, water (100 ml) was added and the product was extracted with dichloromethane (2*100 ml). The organic phases were combined and washed with brine (60 ml), dried (sodium sulfate), filtered and evaporated in vacuo. Purification by chromatography on silica gel using heptan:ethyl acetate:acetic acid (10:10:1) as gradient and azeotropic destillation with toluen gave 2.78 g (yield 79%) of (S)-2-ethoxy-3-[4-(2-{4-methanesulfonyloxyphenyl}ethoxy)phenyl]propanoic acid. ¹H-NMR (600 MHz; DMSO-d₆): δ 1.02 (t, 3H, J=7.0 Hz), 2.78 (dd, 1H, J=13.9 and 8.0 Hz), 2.86 (dd, 1H, J=13.9 and 5.2 Hz), 3.04 (t, 2H, J=6.8 Hz), 3.28 (dq, 1H, J329.1 and 7.0 Hz), 3.35 (s, 3H), 3.49 (dq, 1H, J=9.1 and 7.0 Hz), 3.92 (dd, 1H, J=5.2 and 7.7 Hz),4.15(t, 2H, J=6.8 Hz), 6.82 (d, 2H, J=8.7 Hz), 7.11 (d, 2H, J=8.7 Hz), 7.27 (d, 2H, J=8.5 Hz), 7.42 (d, 2H, J=8.5 Hz), 12.59 (s, br, 1 OH). ¹³C-NMR (150 MHz; DMSO-d₆): δ 15.2, 34.4, 37.5, 37.7, 65.0, 67.9, 79.4, 114.2, 122.2, 129.6, 130.4, 130.7, 138.0, 147.8, 157.1, 173.4.

References:

AstraZeneca AB US6258850, 2001, B1