Sodium Hydroxide → (R)-6-(3-(2-ethoxyphenoxy)piperidin-1-yl)nicotinic acid

HRID 59902Notes

Reaction equation

[OH-].[Na+].[CH2:3]([O:5][C:6]1[CH:29]=[CH:28][CH:27]=[CH:26][C:7]=1[O:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:25]=[CH:24][C:18]([C:19]([O:21]CC)=[O:20])=[CH:17][N:16]=2)[CH2:10]1)[CH3:4]>O1CCCC1.O>[CH2:3]([O:5][C:6]1[CH:29]=[CH:28][CH:27]=[CH:26][C:7]=1[O:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:25]=[CH:24][C:18]([C:19]([OH:21])=[O:20])=[CH:17][N:16]=2)[CH2:10]1)[CH3:4]

Participants

Conditions

Temperature: 60 °C

Procedure

Aqueous 1N sodium hydroxide solution (27.1 mL, 27.0 mmol) was added to a stirred solution of ethyl (R)-6-(3-(2-ethoxyphenoxy)piperidin-1-yl)nicotinate (2.5 g, 6.8 mmol) in tetrahydrofuran (20 mL) at 0° C. The reaction mixture was heated to 60° C. for 18 h. The mixture was then diluted with water (25 mL) and was washed with ethyl acetate (2×50 mL). The aqueous layer was acidified with citric acid solution (pH-2) and was extracted with ethyl acetate (3×50 mL). The combined organics were dried over sodium sulfate, filtered and concentrated. The crude solid material was purified by washing with ether and hexane to afford (R)-6-(3-(2-ethoxyphenoxy)piperidin-1-yl)nicotinic acid (2.3 g) as white solid. 1H NMR (400 MHz, DMSO-d6) δ 12.39 (s, 1H), 8.57 (d, 1H), 7.87 (dd, 1H), 7.03 (dd, 1H), 6.90 (m, 3H), 6.79 (d, 1H), 4.29 (m, 1H), 4.16 (m, 1H), 3.91 (m, 2H), 3.76 (m, 1H), 3.59 (m, 2H), 2.01 (m, 1H), 1.81 (m, 2H), 1.51 (m, 1H), 1.23 (t, 3H). MS (ES+) 343.2 (M+H).

Workup

washwas washed with ethyl acetate (2×50 mL)
extractionwas extracted with ethyl acetate (3×50 mL)
dry with materialThe combined organics were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe crude solid material was purified
washby washing with ether and hexane

Sources & evidence

ORD record: ord-3d9b30a07a5e435eb0a101dd861e4d38
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440949B2

Reaction notes

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