Sodium Carbonate → HCID 68948397, compound

HRID 2384862Notes

Reaction equation

HRID 2384862 reaction equation
I[C:2]1[C:10]2[CH2:9][CH2:8][O:7][C:6](=[O:11])[C:5]=2[S:4][CH:3]=1.[CH3:12]B(O)O.C([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO.O.C(COC)OC>[CH3:12][C:2]1[C:10]2[CH2:9][CH2:8][O:7][C:6](=[O:11])[C:5]=2[S:4][CH:3]=1

Participants

11

Reactant 6

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 139377Methylboronic AcidHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 68949967HCID 68949967, compound

Product 1

HCID 68948397HCID 68948397, compoundYield 22.1%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Mix 3-iodo-4,5-dihydro-thieno[2,3-c]pyran-7-one (1.0, 3.57 mmol) and methyl boronic acid (428 mg, 7.14 mmol) in 7:3:1 dimethoxyethane:water:EtOH (10 mL) and add 2.0 M Na2CO3 (3.5 mL). Bubble dry argon gas through the reaction mixture for 10-15 min to remove oxygen. Add Pd(PPh3)4 (210 mg, 0.18 mmol) and heat using microwave irradiation to 130° C. for 45 min. Pour into 1 N NaOH (50 mL) and wash with hexanes (50 mL). Acidify the aqueous layer with 5N HCl until pH=1 and extract with EtOAc (3×50 mL). Wash the combined organic extracts with brine (50 mL). Concentrate, then add toluene (35 mL) to the crude intermediate. Add p-toluenesulfonic acid monohydrate (339 mg, 1.8 mmol) and heat to 80° C. overnight. Cool to RT, pour into aqueous NaHCO3 (100 mL) and extract with EtOAc (3×100 mL). Wash the combined extracts with brine (100 mL). Dry the organic portion, filter and concentrate. Purify using silica gel chromatography (0-50% EtOAc/hexanes) to provide 133 mg (22%) of the desired product. ES/MS m/z 169.3 [M+H]+.

Workup

  1. customBubble dry argon gas through the reaction mixture for 10-15 min
  2. customto remove oxygen
  3. custommicrowave irradiation to 130° C. for 45 min
  4. washwash with hexanes (50 mL)
  5. extractionextract with EtOAc (3×50 mL)
  6. washWash the combined organic extracts with brine (50 mL)
  7. concentrationConcentrate
  8. extractionextract with EtOAc (3×100 mL)
  9. washWash the combined extracts with brine (100 mL)
  10. customDry the organic portion
  11. filtrationfilter
  12. concentrationconcentrate
  13. customPurify

Sources & evidence

ORD record
ord-9a12701548ca49af9d7d214a915e40d5
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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