Water → (trans)-Benzyl 3-fluoro-4-(quinolin-8-yloxy)piperidine-1-carboxylate

HRID 1095733Notes

Reaction equation

Cl.Cl.[F:3][C@H:4]1[C@H:9]([O:10][C:11]2[CH:12]=[CH:13][CH:14]=[C:15]3[C:20]=2[N:19]=[CH:18][CH:17]=[CH:16]3)[CH2:8][CH2:7][NH:6][CH2:5]1.[C:21](Cl)(=[O:30])[O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.O.C(OCC)(=O)C>C(Cl)Cl>[F:3][C@H:4]1[C@H:9]([O:10][C:11]2[CH:12]=[CH:13][CH:14]=[C:15]3[C:20]=2[N:19]=[CH:18][CH:17]=[CH:16]3)[CH2:8][CH2:7][N:6]([C:21]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:30])[CH2:5]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a 0° C. solution of 8-((trans)-3-fluoropiperidin-4-yloxy)quinoline dihydrochloride (6.6 g, 26.8 mmol) and TEA (18.7 ml, 134.0 mmol) in 134 mL DCM was added benzyl carbonochloridate (4.4 ml, 29.5 mmol). The reaction mixture was stirred 15 minutes at 0° C., then warmed to ambient temperature and stirred another 16 hours. Water was added, and the mixture was extracted with DCM. The combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was purified on silica gel (Biotage 40M, loaded with 4:1hexanes:ethyl acetate and 500 mL flushed, then gradient to 1:1 hexanes:ethyl acetate) to give (trans)-benzyl 3-fluoro-4-(quinolin-8-yloxy)piperidine-1-carboxylate (5.2 g, 13.67 mmol, 51.01% yield) as an oil. MS APCI (+) m/z 381 (M+1) detected.

Workup

temperaturewarmed to ambient temperature
stirringstirred another 16 hours
extractionthe mixture was extracted with DCM
dry with materialThe combined extracts were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe crude was purified on silica gel (Biotage 40M
custom1hexanes:ethyl acetate and 500 mL flushed

Sources & evidence

ORD record: ord-bc5124347f9c4c78829e11451846c48d
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08138181B2

Reaction notes

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