Water → 1-(6-Hydroxy-3-(trifluoromethyl)quinolin-2-yl)piperidine-4-carboxylic acid

HRID 1410596Notes

Reaction equation

C[O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([N:13]1[CH2:18][CH2:17][CH:16]([C:19]([O:21]C)=[O:20])[CH2:15][CH2:14]1)[C:7]([C:23]([F:26])([F:25])[F:24])=[CH:6]2.B(Br)(Br)Br.O>C(Cl)Cl>[OH:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([N:13]1[CH2:18][CH2:17][CH:16]([C:19]([OH:21])=[O:20])[CH2:15][CH2:14]1)[C:7]([C:23]([F:26])([F:25])[F:24])=[CH:6]2

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methyl 1-(6-methoxy-3-(trifluoromethyl)quinolin-2-yl)piperidine-4-carboxylate (300 mg, 0.815 mmol) in DCM (5 mL) was added BBr3 (0.4 mL, 4.08 mmol) dropwise at 0° C. The mixture was stirred at 0° C. for 20 hours. Water (10 mL) was added to the mixture dropwise at 0° C. The mixture was concentrated in vacuo, then diluted with EtOAc (150 mL), filtered and concentrated in vacuo. Purification by prep-HPLC (0.1% TFA as additive) to give Compound 41 (26 mg, yield 9.4%) as a solid. 1H NMR (MeOD 400 MHz): δ 8.51 (s, 1H), 7.82 (d, J=8.8 Hz, 1H), 7.41 (dd, J=8.8, 2.8 Hz, 1H), 7.21 (d, J=2.8 Hz, 1H), 3.55-3.49 (m, 2H), 3.13-3.02 (m, 2H), 2.58-2.49 (m, 1H), 2.09-2.00 (m, 2H), 1.93-1.82 (m, 2H). MS (ESI): m/z 340.7 [M+H]+.

Workup

concentrationThe mixture was concentrated in vacuo
additiondiluted with EtOAc (150 mL)
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by prep-HPLC (0.1% TFA as additive)

Sources & evidence

ORD record: ord-69f0db026f1a4ef68fbe26dacca25989
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08921562B2

Reaction notes

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