Tert-Butyl nitrite → 4,6-Dibromo-2-(2-chloro-4-fluorophenyl)-3-methylpyridine

HRID 394175Notes

Reaction equation

[Br:1][C:2]1[C:7](N)=[C:6]([Br:9])[C:5]([CH3:10])=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[Cl:18])[N:3]=1.C(ON=O)(C)(C)C>C1COCC1>[Br:9][C:6]1[CH:7]=[C:2]([Br:1])[N:3]=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=2[Cl:18])[C:5]=1[CH3:10]

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred solution of 2,4-dibromo-6-(2-chloro-4-fluorophenyl)-5-methylpyridin-3-amine (4.8 g, 12.2 mmol, 1 eq) in THF (50 mL) was added tert-butylnitrite (2.2 mL, 18.25 mmol, 1.5 eq). The mixture was warmed to 60° C. and mild gas evolution was observed. After 1.75 h the heating bath was turned off and the mixture was allowed to stir overnight. Additional tert-butylnitrite (1 mL) was added and the mixture was again warmed to 60° C. After 2 h no starting material was left as assessed by HPLC analysis. The mixture was cooled and the solvent removed under reduced pressure. The product was purified by flash column chromatography on silica gel eluting with 2% Et2O in hexanes to give 4,6-dibromo-2-(2-chloro-4-fluorophenyl)-3-methylpyridine. Mass spectrum (ESI) 378.0 (M+1); 380.0 (M+3); 382.0 (M+5).

Workup

temperaturethe mixture was again warmed to 60° C
waitAfter 2 h no starting material was left
temperatureThe mixture was cooled
customthe solvent removed under reduced pressure
customThe product was purified by flash column chromatography on silica gel eluting with 2% Et2O in hexanes

Sources & evidence

ORD record: ord-002d1e73025c4b0cbbd758e2ac8236e6
Source dataset: uspto-grants-2004_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06809199B2

Reaction notes

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