Water → methyl (R)-6-(3-(2-ethoxyphenoxy)piperidin-1-yl)-5-fluoronicotinate

HRID 59903Notes

Reaction equation

C(N(CC)CC)C.[CH2:8]([O:10][C:11]1[CH:23]=[CH:22][CH:21]=[CH:20][C:12]=1[O:13][C@@H:14]1[CH2:19][CH2:18][CH2:17][NH:16][CH2:15]1)[CH3:9].Cl[C:25]1[C:34]([F:35])=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[CH:27][N:26]=1.O>C(#N)C>[CH2:8]([O:10][C:11]1[CH:23]=[CH:22][CH:21]=[CH:20][C:12]=1[O:13][C@@H:14]1[CH2:19][CH2:18][CH2:17][N:16]([C:25]2[C:34]([F:35])=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[CH:27][N:26]=2)[CH2:15]1)[CH3:9]

Participants

Conditions

Temperature: 50 °C

Procedure

Triethylamine (0.45 mL, 3.3 mmol) was added to a stirred solution of (R)-3-(2-ethoxy-phenoxy)-piperidine (0.41 g, 1.6 mmol) and methyl 6-chloro-5-fluoronicotinate (0.30 g, 1.6 mmol) in acetonitrile (15 mL) at 0° C. The reaction mixture was heated at 50° C. for 18 h. The mixture was cooled to ambient temperature, water (30 mL) was added, and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography (30% ethyl acetate-hexanes) to afford methyl (R)-6-(3-(2-ethoxyphenoxy)piperidin-1-yl)-5-fluoronicotinate (0.40 g). MS (ES+) 375.2 (M+H).

Workup

temperatureThe mixture was cooled to ambient temperature
extractionthe mixture was extracted with ethyl acetate (3×50 mL)
dry with materialThe combined organic layers were dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe crude material was purified by column chromatography (30% ethyl acetate-hexanes)

Sources & evidence

ORD record: ord-289fb72dd912409b99240efd16ec4903
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440949B2

Reaction notes

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