Lithium Bromide → 2-(3,4-Difluorophenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid

HRID 1963132Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][CH:13]([C:15]([O:17]C)=[O:16])[CH2:12][CH2:11][N:10]2[C:19]([O:21][CH3:22])=[O:20])[CH:5]=[CH:6][C:7]=1[F:8].[Br-].[Li+]>C1COCC1.O>[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][CH:13]([C:15]([OH:17])=[O:16])[CH2:12][CH2:11][N:10]2[C:19]([O:21][CH3:22])=[O:20])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

Conditions

Temperature: 80 °C

Procedure

Dimethyl 2-(3,4-difluorophenyl)piperidine-1,4-dicarboxylate (6.578 g, 21.00 mmol) was dissolved in THF (40 mL) and water (0.800 mL). Lithium bromide (14.59 g, 167.97 mmol) and TEA (11.71 mL, 83.98 mmol) were added and the reaction was stirred at 80° C. for 3 h. The reaction mixture was cooled to room temperature and some solvent evaporated in vacuo. EtOAc (150 mL) and water (150 mL) were added, shaken and the phases separated. The organic phase was extracted with water (150 mL). The combined aqueous phases were acidified with 3 M HCl to pH 1 and extracted with EtOAc (2×300 mL). The combined organic phases were dried with Na2SO4, filtered and evaporated in vacuo to yield 2-(3,4-difluorophenyl)-1-(methoxycarbonyl)piperidine-4-carboxylic acid (5.66 g, 90%) as a light brown oil. MS m/z 298 (M+H)+.

Workup

temperatureThe reaction mixture was cooled to room temperature
customsome solvent evaporated in vacuo
additionEtOAc (150 mL) and water (150 mL) were added
stirringshaken
customthe phases separated
extractionThe organic phase was extracted with water (150 mL)
extractionextracted with EtOAc (2×300 mL)
dry with materialThe combined organic phases were dried with Na2SO4
filtrationfiltered
customevaporated in vacuo

Sources & evidence

ORD record: ord-ff96c9fb2dbb4ef68464ee356d548ee0
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415378B2

Reaction notes

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