Dichloromethane → (1RS,2SR,6RS,7SR)-4-(3-ethyl-4'-fluorobiphen-4-yl)-10-oxatricyclo[5.2.1.02,6]decane-3,5-dione

HRID 1430766Notes

Reaction equation

HRID 1430766 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:16](=[O:17])[CH:15]3[CH:10]([CH:11]4[O:18][CH:14]3[CH2:13][CH2:12]4)[C:9]2=[O:19])=[C:4]([CH2:20][CH3:21])[CH:3]=1.[F:22][C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.[F-].[Cs+].ClCCl>COCCOC>[CH2:20]([C:4]1[C:5]([CH:8]2[C:16](=[O:17])[CH:15]3[CH:10]([CH:11]4[O:18][CH:14]3[CH2:13][CH2:12]4)[C:9]2=[O:19])=[CH:6][CH:7]=[C:2]([C:26]2[CH:27]=[CH:28][C:23]([F:22])=[CH:24][CH:25]=2)[CH:3]=1)[CH3:21]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 25953Cesium fluorideHCID 2856454-Fluorophenylboronic acidHCID 67283612(1RS,2SR,6RS,7SR)-4-(4-bromo-2-ethylphenyl)-10-oxatricyclo-[5.2.1.02,6]decane-3,5-dione

Product 1

HCID 77736178(1RS,2SR,6RS,7SR)-4-(3-ethyl-4'-fluorobiphen-4-yl)-10-oxatricyclo[5.2.1.02,6]decane-3,5-dione

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (1RS,2SR,6RS,7SR)-4-(4-bromo-2-ethylphenyl)-10-oxatricyclo-[5.2.1.02,6]decane-3,5-dione (200 mg, 0.57 mmol), 4-fluorophenylboronic acid (112 mg, 0.80 mmol) and cesium fluoride (260 mg, 1.71 mmol) are stirred together in degassed 1,2-dimethoxyethane (5 ml) at room temperature under an atmosphere of nitrogen for 40 minutes at room temperature. [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (74 mg, 0.09 mmol) is added, and the reaction mixture is heated to 80° C. for 20 hours. The mixture is cooled to room temperature, filtered through a plug of diatomaceous earth, washing with 2M aqueous hydrochloric acid and dichloromethane. The organic phase is collected, and the aqueous phase is extracted with dichloromethane. The organic solutions are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure. The residue is purified by column choramtography on silica gel to give (1RS,2SR,6RS,7SR)-4-(3-ethyl-4′-fluorobiphen-4-yl)-10-oxatricyclo[5.2.1.02,6]decane-3,5-dione.

Workup

  1. temperatureThe mixture is cooled to room temperature
  2. filtrationfiltered through a plug of diatomaceous earth
  3. washwashing with 2M aqueous hydrochloric acid and dichloromethane
  4. customThe organic phase is collected
  5. extractionthe aqueous phase is extracted with dichloromethane
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate is concentrated under reduced pressure
  9. customThe residue is purified by column choramtography on silica gel

Sources & evidence

ORD record
ord-10f2b57525c143a8bb0ed7a50a93901e
Source dataset
uspto-grants-2015_01
Patent number
US08940913B2

Reaction notes

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