alpha-Bromo-o-fluorotoluene → Ethyl 1-benzyl-4-(2-fluorobenzyl)piperidine-4-carboxylate

HRID 270042Notes

Reaction equation

[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:29][C:30]1[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=1[CH2:32]Br>O1CCCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([CH2:32][C:31]2[CH:34]=[CH:35][CH:36]=[CH:37][C:30]=2[F:29])([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: -78 °C

Procedure

Ethyl 1-benzylpiperidine-4-carboxylate (2.47 g, 10 mmol) was dissolved in tetrahydrofuran (20 mL) and cooled to −78° C. Lithium bis(trimethylsilyl)amide (11 mL, 1.0 M in tetrahydrofuran) was added slowly, and stirred for 30 minutes. 2-fluoro-benzylbromide (1.34 mL, 11 mmol) in 5 mL tetrahydrofuran was added slowly. The resulting solution was allowed to reach room temperature and stirred over night. The reaction was quenched with ammonium chloride (aq, sat) and partitioned between water and ethyl acetate. The organic layer was washed with brine and dried over magnesium sulphate, filtrated and concentrated. The crude material was purified on silica (heptane/ethyl acetate), to give 2.7 g (77%) the subtitle compound as a colourless oil.

Workup

customto reach room temperature
stirringstirred over night
customThe reaction was quenched with ammonium chloride (aq, sat)
custompartitioned between water and ethyl acetate
washThe organic layer was washed with brine
dry with materialdried over magnesium sulphate
filtrationfiltrated
concentrationconcentrated
customThe crude material was purified on silica (heptane/ethyl acetate)

Sources & evidence

ORD record: ord-8c18a58d889846d2979008f65b8a549d
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07449475B2

Reaction notes

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