Lithium hydroxide, monohydrate → HCID 118366159, compound

HRID 59904Notes

Reaction equation

O.[OH-].[Li+].[CH2:4]([O:6][C:7]1[CH:30]=[CH:29][CH:28]=[CH:27][C:8]=1[O:9][C@@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]2[C:25]([F:26])=[CH:24][C:19]([C:20]([O:22]C)=[O:21])=[CH:18][N:17]=2)[CH2:11]1)[CH3:5]>O1CCCC1.O>[CH2:4]([O:6][C:7]1[CH:30]=[CH:29][CH:28]=[CH:27][C:8]=1[O:9][C@@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]2[C:25]([F:26])=[CH:24][C:19]([C:20]([OH:22])=[O:21])=[CH:18][N:17]=2)[CH2:11]1)[CH3:5]

Participants

Conditions

Temperature: 22.5 °C

Procedure

Lithium hydroxide hydrate (62 mg, 2.6 mmol) was added to a solution of methyl (R)-6-(3-(2-ethoxyphenoxy)piperidin-1-yl)-5-fluoronicotinate (0.65 g, 1.7 mmol) in tetrahydrofuran (8 mL) and water (8 mL), and the resulting solution was stirred at 20-25° C. for 18 h. The mixture was then diluted with water (20 mL) and was washed with ethyl acetate (2×30 mL). The aqueous layer was acidified with citric acid solution (pH-2) and was extracted with ethyl acetate (3×30 mL). The combined organics were dried over sodium sulfate, filtered, and concentrated to afford (R)-6-(3-(2-ethoxyphenoxy)piperidin-1-yl)-5-fluoronicotinic acid as a white solid (0.50 g). 1H NMR (400 MHz, DMSO-d6) δ 12.85 (br s, 1H), 8.46 (s, 1H), 7.68 (dd, 1H), 7.00 (dd, 1H), 6.87 (m, 3H), 4.39 (m, 1H), 4.02 (dd, 1H), 3.89 (m, 2H), 3.68 (m, 3H), 1.97 (m, 2H), 1.79 (m, 1H), 1.55 (m, 1H), 1.22 (t, 3H). MS (ES+) 361.2 (M+H).

Workup

washwas washed with ethyl acetate (2×30 mL)
extractionwas extracted with ethyl acetate (3×30 mL)
dry with materialThe combined organics were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-adf0ffe014fb409cb96e4ba64ffab24b
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440949B2

Reaction notes

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