Hydrochloric Acid → (1RS,2SR,6RS,7RS)-8-(4-fluorophenyl)-4-(2,4,6-trimethylphenyl)-10-oxatricyclo[5.2.1.02,6]dec-8-en-3,5-dione

HRID 407857Notes

Reaction equation

HRID 407857 reaction equation
Br[C:2]1[CH:3]2[O:11][CH:9]([CH:10]=1)[CH:8]1[CH:4]2[C:5](=[O:22])[CH:6]([C:13]2[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[CH:15][C:14]=2[CH3:21])[C:7]1=[O:12].[F:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=C(S([O-])(=O)=O)C=2OC)CCCCC1.[Na+].P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[CH:3]3[O:11][CH:9]([CH:10]=2)[CH:8]2[CH:4]3[C:5](=[O:22])[CH:6]([C:13]3[C:14]([CH3:21])=[CH:15][C:16]([CH3:20])=[CH:17][C:18]=3[CH3:19])[C:7]2=[O:12])=[CH:26][CH:25]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 2856454-Fluorophenylboronic acidHCID 23693092Sodium 2'-(dicyclohexylphosphanyl)-2,6-dimethoxy(1,1'-biphenyl)-3-sulfonate--water (1/1/1)HCID 67284125(1RS, 2RS,6SR,7SR)-8-bromo-4-(2,4,6-trimethylphenyl)-10-oxatricyclo-[5.2.1.02,6]dec-8-en-3,5-dione

Product 1

HCID 67283881(1RS,2SR,6RS,7RS)-8-(4-fluorophenyl)-4-(2,4,6-trimethylphenyl)-10-oxatricyclo[5.2.1.02,6]dec-8-en-3,5-dione

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of (1RS,2RS,6SR,7SR)-8-bromo-4-(2,4,6-trimethylphenyl)-10-oxatricyclo-[5.2.1.02,6]dec-8-en-3,5-dione (300 mg, 0.82 mmol), 4-fluorophenylboronic acid (171 mg, 1.22 mmol), sodium 2′-dicyclohexylphosphino-2,6-dimethoxy-1,1-biphenyl-3-sulfonate hydrate (17 mg, 0.03 mmol), potassium phosphate (522 mg, 2.5 mmol) and palladium acetate (4 mg, 0.02 mmol) in water (8 ml) are heated for 150° C. for 25 minutes under microwave irradiation. The mixture is cooled to room temperature and dilute aqueous hydrochloric acid is added. The mixture is filtered and the filtrate is extracted with ethyl acetate. The organic extracts are combined, dried over anhydrous magnesium sulfate, filtered and the filtrate is concentrated under reduced pressure. Purification by column chromatography on silica gel gives (1RS,2SR,6RS,7RS)-8-(4-fluorophenyl)-4-(2,4,6-trimethylphenyl)-10-oxatricyclo[5.2.1.02,6]dec-8-en-3,5-dione.

Workup

  1. temperatureThe mixture is cooled to room temperature
  2. filtrationThe mixture is filtered
  3. extractionthe filtrate is extracted with ethyl acetate
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate is concentrated under reduced pressure
  7. customPurification by column chromatography on silica gel

Sources & evidence

ORD record
ord-3cbf642752874ed7bf5be552f8d94916
Source dataset
uspto-grants-2014_06
Patent number
US08754242B2

Reaction notes

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