8-Hydroxyquinoline → (trans)-Tert-butyl 3-fluoro-4-(quinolin-8-yloxy)piperidine-1-carboxylate

HRID 1095731Notes

Reaction equation

[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[OH:11])[CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:18][C@H:19]1[C@@H:24](OS(C)(=O)=O)[CH2:23][CH2:22][N:21]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:20]1.C(Cl)Cl>CN(C=O)C.CCOC(C)=O>[F:18][C@H:19]1[C@H:24]([O:11][C:9]2[CH:8]=[CH:7][CH:6]=[C:5]3[C:10]=2[N:1]=[CH:2][CH:3]=[CH:4]3)[CH2:23][CH2:22][N:21]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:20]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of quinolin-8-ol (3.50 g, 24.1 mmol) in 60 mL DMF was added cesium carbonate (23.6 g, 72.3 mmol), followed by (cis)-tert-butyl 3-fluoro-4-(methylsulfonyloxy)piperidine-1-carboxylate (8.24 g, 27.7 mmol). The reaction mixture was heated in a 100° C. sand bath and stirred 20 hours. The reaction mixture was cooled to ambient temperature, filtered through GF/F paper topped with compressed Celite, rinsed with DMF, and concentrated. The crude was purified on silica gel (Biotage 40M, 9:1 DCM:EtOAc until the product eluted, then 2:1 DCM:EtOAc) to give (trans)-tert-butyl 3-fluoro-4-(quinolin-8-yloxy)piperidine-1-carboxylate (0.701 g, 2.02 mmol, 42% yield). LC/MS ESI (+) m/z 347 (M+1) detected.

Workup

temperatureThe reaction mixture was cooled to ambient temperature
filtrationfiltered through GF/F paper
washrinsed with DMF
concentrationconcentrated
customThe crude was purified on silica gel (Biotage 40M, 9:1 DCM
washEtOAc until the product eluted

Sources & evidence

ORD record: ord-d5219f59014f479088762387c66ff254
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08138181B2

Reaction notes

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