18-Crown-6 → 2-[(5-Bromo-4-fluoro-2-nitrophenyl)oxy]-1-chloro-3-fluoro-4-methylbenzene

HRID 1875198Notes

Reaction equation

HRID 1875198 reaction equation
[Cl:1][C:2]1[C:7]([OH:8])=[C:6]([F:9])[C:5]([CH3:10])=[CH:4][CH:3]=1.C1OCCOCCOCCOCCOCCOC1.CC(C)([O-])C.[K+].[Br:35][C:36]1[CH:41]=[C:40](F)[C:39]([N+:43]([O-:45])=[O:44])=[CH:38][C:37]=1[F:46]>CS(C)=O.CCOC(C)=O>[Br:35][C:36]1[C:37]([F:46])=[CH:38][C:39]([N+:43]([O-:45])=[O:44])=[C:40]([O:8][C:7]2[C:6]([F:9])=[C:5]([CH3:10])[CH:4]=[CH:3][C:2]=2[Cl:1])[CH:41]=1

Participants

7

Reactant 4

HCID 2855718-Crown-6HCID 27362864-Bromo-2,5-difluoronitrobenzeneHCID 27736846-Chloro-2-fluoro-3-methylphenolHCID 23665647Potassium tert-butoxide

Product 1

HCID 684871652-[(5-Bromo-4-fluoro-2-nitrophenyl)oxy]-1-chloro-3-fluoro-4-methylbenzeneYield 71%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-chloro-2-fluoro-3-methylphenol (12.8 g, 80 mmol) and 18-crown-6 (4.21 g, 15.94 mmol) in DMSO (100 ml) at 0° C. was added potassium tert-butoxide (1.0 M solution in THF) (80 ml, 80 mmol) and the reaction mixture was stirred at RT for 30 minutes. Next, 1-bromo-2,5-difluoro-4-nitrobenzene (19.4 g, 80 mmol) was added dropwise (in solution of 60 mL DMSO) and the reaction mixture was stirred overnight at RT. The reaction mixture was diluted with EtOAc and washed with water. The solvent was removed and the crude material was triturated with methanol to give 2-[(5-bromo-4-fluoro-2-nitrophenyl)oxy]-1-chloro-3-fluoro-4-methylbenzene (21.3 g, 56.3 mmol, 71% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.26 (d, 1H), 7.34-7.40 (m, 1H), 7.21-7.34 (m, 2H), 2.23 (d, 3H).

Workup

  1. stirringthe reaction mixture was stirred overnight at RT
  2. washwashed with water
  3. customThe solvent was removed
  4. customthe crude material was triturated with methanol

Sources & evidence

ORD record
ord-aff3195a2bac40af98de59828479ad8d
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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