Potassium Hydroxide → 1,4-Difluoro-2-(3-fluoro-benzyloxy)-5-nitrobenzene

HRID 1823012Notes

Reaction equation

HRID 1823012 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].COCCOCCN(CCOCCOC)CCOCCOC.[OH-].[K+].[F:34][C:35]1[CH:40]=[C:39](F)[C:38]([F:42])=[CH:37][C:36]=1[N+:43]([O-:45])=[O:44]>C(OCC)(=O)C.O>[F:42][C:38]1[CH:37]=[C:36]([N+:43]([O-:45])=[O:44])[C:35]([F:34])=[CH:40][C:39]=1[O:6][CH2:5][C:4]1[CH:7]=[CH:8][CH:9]=[C:2]([F:1])[CH:3]=1

Participants

7

Reactant 4

HCID 14797Potassium HydroxideHCID 680083-Fluorobenzylic alcoholHCID 750121,2,4-Trifluoro-5-nitrobenzeneHCID 112414Ethanamine, 2-(2-methoxyethoxy)-N,N-bis[2-(2-methoxyethoxy)ethyl]-

Product 1

HCID 219200371,4-Difluoro-2-(3-fluoro-benzyloxy)-5-nitrobenzeneYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2.35 g (18.6 mmol) of 3-fluorobenzylalcohol and 0.55 g (1.7 mmol) of tris[2-(2-methoxyethoxy)ethyl]amine is treated portionwise under stirring with 1.06 g (18.6 mmol) of potassium hydroxide. Stirring is continued for 10 min if necessary under slight heating to reach a homogenous reaction mixture. Thereafter, 3.0 g (16.9 mmol) of 2,4,5-trifluoronitrobenzene are added dropwise. The reaction mixture becomes solid and is heated to 100° C. for 2 hours. For the working-up, the mixture is cooled to RT, then 25 ml water and 25 ml ethyl acetate are added and stirring continued for 30 min. The organic layer is separated and the aqueous layer is extracted twice with ethyl acetate. The combined organic layers are washed with water, then twice with 2N hydrochloric acid and finally with water. After drying over magnesium sulfate, the solution is evaporated under reduced pressure. During evaporation, the byproduct, 1-fluoro-2,4-bis-(3-fluoro-benzyloxy)-5-nitro-benzene precipitates. For purification, the material obtained is chromatographed on silica gel using a 4:1-mixture of n-hexane and ethyl acetate as the eluent. There are obtained 2.63 g (55% of theory) of the 1,4-difluoro-2-(3-fluoro-benzyloxy)-5-nitro-benzene as an off-white solid. MS: m/e=283 (M)+.

Workup

  1. additionis treated portionwise
  2. temperatureif necessary under slight heating
  3. temperaturethe mixture is cooled to RT
  4. stirringstirring
  5. waitcontinued for 30 min
  6. customThe organic layer is separated
  7. extractionthe aqueous layer is extracted twice with ethyl acetate
  8. washThe combined organic layers are washed with water
  9. dry with materialAfter drying over magnesium sulfate
  10. customthe solution is evaporated under reduced pressure
  11. customDuring evaporation
  12. customthe byproduct, 1-fluoro-2,4-bis-(3-fluoro-benzyloxy)-5-nitro-benzene precipitates
  13. customFor purification
  14. customthe material obtained
  15. customis chromatographed on silica gel using a 4

Sources & evidence

ORD record
ord-62133927573b4d8cb8f506fdec3fd480
Source dataset
uspto-grants-2006_05
Patent number
US07037935B2

Reaction notes

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