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

HRID 1430763Notes

Reaction equation

HRID 1430763 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:22][CH3:23])=[C:6]([CH:8]2[C:16](=[O:17])[CH:15]3[CH:10]([C:11]4([CH3:20])[O:18][C:14]3([CH3:19])[CH:13]=[CH:12]4)[C:9]2=[O:21])[CH:7]=1.[Cl:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[C:27]([F:34])[CH:26]=1.[F-].[Cs+]>COCCOC.ClCCl>[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([C:2]2[CH:3]=[CH:4][C:5]([CH2:22][CH3:23])=[C:6]([CH:8]3[C:9](=[O:21])[CH:10]4[CH:15]([C:14]5([CH3:19])[O:18][C:11]4([CH3:20])[CH2:12][CH2:13]5)[C:16]3=[O:17])[CH:7]=2)=[C:27]([F:34])[CH:26]=1

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 67284135(1RS,2SR,6RS,7SR)-4-(5-bromo-2-ethylphenyl)-1,7-dimethyl-10-oxatricyclo[5.2.1.02,6]dec-8-en-3,5-dione

Product 1

HCID 131732374(1RS,2SR,6RS,7SR)-4-(4'-chloro-4-ethyl-2'-fluorobiphen-3-yl)-1,7-dimethyl-10-oxatricyclo-[5.2.1.02,6]decane-3,5-dione

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

A mixture of (1RS,2SR,6RS,7SR)-4-(5-bromo-2-ethylphenyl)-1,7-dimethyl-10-oxatricyclo[5.2.1.02,6]dec-8-en-3,5-dione (113 mg, 0.3 mmol), 4-chloro-2-fluorophenylboronic acid (103 mg, 0.6 mmol) and cesium fluoride (449 mg, 3.0 mmol) in degassed 1,2-dimethoxyethane (1.5 ml) are stirred under nitrogen at room temperature for 40 minutes. [1,1′-bis(diphenylphosphino) ferrocene]dichloropalladium(II) complex with dichloromethane (48 mg, 0.06 mmol) is added, followed by a further quantity of 1,2-dimethoxyethane (1 ml) and reaction mixture is heated to 80° C. for 18 hours. The mixture is cooled to room temperature, then diluted with dichloromethane and filtered through a small plug of diatomaceous earth. The filtrate is evaporated and the residue is purified by column chromatography on silica gel, to give (1RS,2SR,6RS,7SR)-4-(4′-chloro-4-ethyl-2′-fluorobiphen-3-yl)-1,7-dimethyl-10-oxatricyclo-[5.2.1.02,6]decane-3,5-dione.

Workup

  1. temperatureis heated to 80° C. for 18 hours
  2. temperatureThe mixture is cooled to room temperature
  3. filtrationfiltered through a small plug of diatomaceous earth
  4. customThe filtrate is evaporated
  5. customthe residue is purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-810d144a71ab4006b5455948c959be0e
Source dataset
uspto-grants-2015_01
Patent number
US08940913B2

Reaction notes

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