1-(Bromomethyl)-2,4-difluorobenzene → HCID 19365952, compound

HRID 1736414Notes

Reaction equation

HRID 1736414 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH2:4]Br.[Mg].CON(C)[C:15](=[O:23])[C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[N:18][CH:17]=1>C(OCC)C.C1COCC1>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([C:15](=[O:23])[CH2:4][C:3]2[CH:6]=[CH:7][C:8]([F:10])=[CH:9][C:2]=2[F:1])=[CH:17][N:18]=1

Participants

6

Reactant 3

HCID 902971-(Bromomethyl)-2,4-difluorobenzeneHCID 5462224MagnesiumHCID 114355976-Chloro-N-methoxy-N-methylnicotinamide

Product 1

HCID 19365952HCID 19365952, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

2,4-Difluorobenzyl bromide (9.0 ml, 70 mmol) was added dropwise to a suspension of magnesium (1.8 g, 75 mmol) in diethyl ether (50 ml) under an atmosphere of dry nitrogen at a sufficient rate to maintain a gentle reflux. The resulting solution was stirred for 15 minutes at room temperature and was then added dropwise to a solution of the product of part (i) (10.0 g, 50 mmol) in THF (70 ml) at -70° C. under an atmosphere of nitrogen. The mixture was warmed to room temperature, stirred for 2 hours then quenched with dilute hydrochloric acid (2M, 50 ml). The layers were separated and the aqueous phase was extracted with diethyl ether (2×50 ml). The combined extracts were dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash chromatography on silica by elution with ether/hexane (1:1). The appropriate fractions were combined, evaporated under reduced pressure and the crude product was triturated with diethyl ether to give the title compound as a yellow solid, (10.7 g), m.p. 93°-95° C. Found: C,58.01; H,2.99; N,5.17; C13H8ClF2NO requires: C,58.33; H,3.01; N,5.23%.

Workup

  1. temperatureto maintain a gentle reflux
  2. temperatureThe mixture was warmed to room temperature
  3. stirringstirred for 2 hours
  4. customthen quenched with dilute hydrochloric acid (2M, 50 ml)
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted with diethyl ether (2×50 ml)
  7. dry with materialThe combined extracts were dried (MgSO4)
  8. customevaporated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica by elution with ether/hexane (1:1)
  10. customevaporated under reduced pressure
  11. customthe crude product was triturated with diethyl ether

Sources & evidence

ORD record
ord-6ed50a7d919e4de29fb1d21520a2316c
Source dataset
uspto-grants-1996_07
Patent number
US05541203

Reaction notes

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