3-Fluorobenzyl chloride → 3-[2-(3-fluorophenyl)ethyl]-N(1,1-dimethylethyl)-2-pyridine carboxamide

HRID 569202

Reaction equation

[CH3:1][C:2]([NH:5][C:6]([C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][N:9]=1)=[O:7])([CH3:4])[CH3:3].C([Li])CCC.[Br-].[Na+].[F:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[CH2:26]Cl>O1CCCC1.O>[F:22][C:23]1[CH:24]=[C:25]([CH2:26][CH2:14][C:13]2[C:8]([C:6]([NH:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])=[N:9][CH:10]=[CH:11][CH:12]=2)[CH:28]=[CH:29][CH:30]=1

Participants

Conditions

Temperature: -40 °C

Procedure

Tetrahydrofuran (125 mL), and N-(1,1-dimethylethyl)-3-methyl-2-pyridine carboxamide (1 equivalent), are charged and cooled to -40° C. under nitrogen. Two equivalents of n-butyllithium are then added over 40 minutes. When half the n-butyllithium is added the mixture turns purple. Sodium bromide (1.3 g) is added and 3-fluoro-benzyl chloride (1.05 equivalents) is added dropwise (1:1 solution in tetrahydrofuran) over 40-50 minutes while the temperature is maintained at -40° C. After 30 minutes at -40° C., the mixture is diluted with water (250 mL) and the organic phase separated. This phase is dried over sodium sulphate and the solvent removed yielding an oil from which solid product, 3-[2-( 3-fluoro-phenyl)ethyl]-N-(1,1-dimethylethyl)-2-pyridine carboxamide, may crystallize.

Workup

temperatureis maintained at -40° C
customthe organic phase separated
dry with materialThis phase is dried over sodium sulphate
customthe solvent removed

Sources & evidence

ORD record: ord-a4373c44ae17434895ae8a9caeb9a1cc
Source dataset: uspto-grants-1988_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04731447

Linked notes

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