Boron tribromide → BenzaMide, 4-(4-ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluoro-

HRID 918965Notes

Reaction equation

HRID 918965 reaction equation
[CH2:1]([C:3]1[C:19]([F:20])=[CH:18][C:6]([O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[CH:10][C:9]=2[F:17])=[C:5]([O:21]C)[CH:4]=1)[CH3:2].B(Br)(Br)Br>ClCCl>[CH2:1]([C:3]1[C:19]([F:20])=[CH:18][C:6]([O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH2:14])=[O:13])=[CH:10][C:9]=2[F:17])=[C:5]([OH:21])[CH:4]=1)[CH3:2]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 51034748HCID 51034748, compound

Product 1

HCID 44208849BenzaMide, 4-(4-ethyl-5-fluoro-2-hydroxyphenoxy)-3-fluoro-Yield 650%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 4-(4-ethyl-5-fluoro-2-methoxyphenoxy)-3-fluorobenzamide (13.31 g, 4.59 mmol; which may be prepared as hereinbefore described for D4) in 130 mL of dichloromethane under argon at −78° C. under intense stirring is added over 15-20 min boron tribromide (130 mL at 1M in dichloromethane). The reaction mixture is warmed up at room temperature under stirring and after 3 h is cooled back to −20° C. for quenching with a saturated aqueous solution of ammonium chloride (100 mL). Partial concentration is performed to remove 170 mL of dichloromethane. 100 mL of ethyl acetate are added. Extraction of the aqueous phase (2*25 mL of ethyl acetate), reunification of the organic phases, aqueous sodium hydrogenocarbonate (200 mL at 1N) wash, drying (Na2SO4) and final concentration affords the crude material which is purified on silicagel (gradient dichloromethane/methanol:100/0→95/5) to afford the title compound 8.75 g (68%).

Workup

  1. temperatureis cooled back to −20° C.
  2. customfor quenching with a saturated aqueous solution of ammonium chloride (100 mL)
  3. concentrationPartial concentration
  4. customto remove 170 mL of dichloromethane
  5. addition100 mL of ethyl acetate are added
  6. extractionExtraction of the aqueous phase (2*25 mL of ethyl acetate), reunification of the organic phases, aqueous sodium hydrogenocarbonate (200 mL at 1N)
  7. washwash
  8. dry with materialdrying (Na2SO4)
  9. concentrationfinal concentration
  10. customaffords the crude material which
  11. customis purified on silicagel (gradient dichloromethane/methanol:100/0→95/5)

Sources & evidence

ORD record
ord-eba9deb3e93144d5af96998beb529f92
Source dataset
uspto-grants-2016_03
Patent number
US09272985B2

Reaction notes

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