Acetic Acid → (e)-11-(Bromomethylene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepine

HRID 244346Notes

Reaction equation

HRID 244346 reaction equation
C(OC(=O)/[CH:5]=[C:6]1/[C:7]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:8]=2[O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]/1=2)C.[OH-].[Li+].C(O)(=O)C.[Br:29]N1C(=O)CCC1=O.S(=O)(O)[O-].[Na+].C(=O)(O)[O-].[Na+]>O.C(O)(C)C>[Br:29]/[CH:5]=[C:6]1/[C:7]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:8]=2[O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]/1=2

Participants

9

Reactant 6

HCID 176Acetic AcidHCID 3939Lithium HydroxideHCID 67184N-bromobutanimideHCID 516892Sodium BicarbonateHCID 23665763Sodium BisulfiteHCID 67333776(E)-(3-Fluoro-6H-dibenzo[b,e]oxepin-11-ylidene)-acetic acid ethyl ester

Product 1

HCID 59468684(e)-11-(Bromomethylene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepineYield 97.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

To a clean, dry 100-gallon reactor with stirring under nitrogen, charge isopropanol (125 L), (E)-(3-fluoro-6H-dibenzo[b,e]oxepin-11-ylidene)-acetic acid ethyl ester (13.857 kg, 46.42 mol), and a solution of lithium hydroxide (3.896 kg, 92.84 mol) in water (54 L). Heat the reaction mixture to 80° C. and stir for 2 h. Cool the reaction mixture to 40° C. and add acetic acid (5.575 kg, 92.84 mol) over 20 min between 40° C. and 45° C. Add N-bromosuccinimide (48.74 mol, 8.676 kg) portion-wise over 30 min at <45° C. Cool the reaction to room temperature and stir for a minimum of 12 h. Add an aqueous solution of sodium bisulfite (−37.7 L) and stir 15 min. Add an aqueous solution of sodium bicarbonate (−37.7 L) and stir 15 min. Add water (129 L) and stir 30 min. Filter to collect the resulting solids, washing with isopropanol:water (1:1, 2×20 L). Dry the solids under vacuum at 32° C. to a constant weight to obtain the title compound (13.8 kg, 97%).

Workup

  1. customTo a clean, dry 100-gallon reactor
  2. stirringstir for 2 h
  3. temperatureCool the reaction mixture to 40° C.
  4. temperatureCool
  5. customthe reaction to room temperature
  6. stirringstir for a minimum of 12 h
  7. stirringstir 15 min
  8. stirringstir 15 min
  9. filtrationFilter
  10. customto collect the resulting solids
  11. washwashing with isopropanol:water (1:1, 2×20 L)
  12. customDry the solids under vacuum at 32° C. to a constant weight

Sources & evidence

ORD record
ord-d4e9be4401e14eb383de8c49d9872a7e
Source dataset
uspto-grants-2014_02
Patent number
US08658638B2

Reaction notes

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