Hydrochloric Acid → HCID 68951087, compound

HRID 2384866Notes

Reaction equation

HRID 2384866 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.I[C:12]1[S:21][C:15]2[C:16](=[O:20])[O:17][CH2:18][CH2:19][C:14]=2[C:13]=1[CH3:22].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Na+].[Na+].Cl.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>CC#N.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:12]2[S:21][C:15]3[C:16](=[O:20])[O:17][CH2:18][CH2:19][C:14]=3[C:13]=2[CH3:22])=[CH:4][CH:3]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 742994-Chlorophenylboronic acidHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 68950943HCID 68950943, compound

Product 1

HCID 68951087HCID 68951087, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

Add 4-chlorophenyl boronic acid (215 mg, 1.38 mmol) to a slurry of 2-iodo-3-methyl-4,5-dihydro-thieno[2,3-c]pyran-7-one (135 mg, 0.46 mmol) in CH3CN (2 mL). Add PPh3 (37 mg, 0.14 mmol) followed by 2.0 M Na2CO3 (0.69 mL). Bubble dry argon through the reaction for 15 min. Add Pd(OAc)2 (12 mg, 0.05 mmol) and heat using microwave irradiation to 100° C. for 45 min. Pour the reaction into 1N HCl (50 mL) and extract with EtOAc (3×50 mL). Wash the combined organic extracts with brine (50 mL). Concentrate, dissolve the crude residue in toluene (5 mL) and treat with p-toluenesulfonic acid monohydrate (50 mg, 0.26 mmol). Heat to 80° C. for 8 h. Cool to RT, pour into aqueous NaHCO3 (50 mL) and extract with EtOAc (3×50 mL). Wash the combined extracts with brine (50 mL) and concentrate. Purify the resulting residue using silica gel chromatography (0-50% EtOAc/hexanes) to provide 111 mg (87%) of the desired product.

Workup

  1. customBubble dry argon
  2. customthrough the reaction for 15 min
  3. custommicrowave irradiation to 100° C. for 45 min
  4. additionPour
  5. extractionextract with EtOAc (3×50 mL)
  6. washWash the combined organic extracts with brine (50 mL)
  7. concentrationConcentrate
  8. dissolutiondissolve the crude residue in toluene (5 mL)
  9. temperatureCool to RT
  10. extractionextract with EtOAc (3×50 mL)
  11. washWash the combined extracts with brine (50 mL)
  12. concentrationconcentrate
  13. customPurify the resulting residue

Sources & evidence

ORD record
ord-d865164d728f4787888c1770698f76c3
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

Loading…