Ethyl Acetate → 2-(4-(4-Ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetic acid

HRID 1050011Notes

Reaction equation

[CH2:1]([O:3][C:4]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[N:7]=[CH:6][C:5]=1[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]([O:29]C)=[O:28])=[C:22]([F:31])[CH:21]=1)[CH3:2].O[Li].O.CC(=O)OCC>C1COCC1.O>[CH2:1]([O:3][C:4]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=2)[N:7]=[CH:6][C:5]=1[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]([OH:29])=[O:28])=[C:22]([F:31])[CH:21]=1)[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of methyl 2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetate (210 g, 519 mmol) in THF (500 mL) was added a solution of LiOH.H2O (52 g, 1.23 mol) in H2O (700 mL). The mixture was stirred at 60° C. for 10 h. TLC (PE/EA=5:1, Rf=0.3) showed the reaction was finished. The mixture was concentrated and neutralized with 1.0 M HCl to pH=7.0. Then the mixture was filtered, and the solid was washed with water and dry in vacuo to give 2-(4-(4-ethoxy-6-((4-methoxybenzyl)oxy)pyridin-3-yl)-2-fluorophenyl)acetic acid (183.3 g, 0.45 mol, 93% yield): 1H NMR (400 MHz, CD3OD) δ 7.94 (s, 1H), 7.41-7.28 (m, 3H), 7.24 (d, J=9.6 Hz, 2H), 6.91 (d, J=8.8 Hz, 2H), 6.44 (s, 1H), 5.26 (s, 2H), 4.11 (q, J=6.8 Hz, 2H), 3.78 (s, 3H), 3.67 (s, 2H), 1.36 (t, J=7.2 Hz, 3H); ES-LCMS m/z 412 (M+H).

Workup

concentrationThe mixture was concentrated
filtrationThen the mixture was filtered
washthe solid was washed with water
customdry in vacuo

Sources & evidence

ORD record: ord-089b708840594895b5ffedcafb9b7443
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382238B2

Reaction notes

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