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

HRID 2351563Notes

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-chromatograph. (3-fluoro-phenyl)ethyl]-N-(l,l-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
customyielding an oil from which solid product
custom(3-fluoro-phenyl)ethyl]-N-(l,l-dimethylethyl)-2-pyridine carboxamide, may crystallize

Sources & evidence

ORD record: ord-764a2cb224384d66b730799578294a6b
Source dataset: uspto-grants-1989_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04873335

Reaction notes

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