Hydrochloric Acid → HCID 69083859, compound

HRID 594373Notes

Reaction equation

HRID 594373 reaction equation
I[C:2]1[C:7]([O:8][CH3:9])=[CH:6][CH:5]=[CH:4][C:3]=1[O:10][CH3:11].[CH:12]([Mg]Cl)(C)C.[CH3:17][C:18]1([CH3:26])[CH2:23][C:22](=[O:24])[O:21][C:20](=[O:25])[CH2:19]1.Cl.[NH4+].[Cl-].C([O-])([O-])=O.[Cs+].[Cs+].IC>C1COCC1.[Cu]I.O.CCOC(C)=O.CN(C=O)C.CCOCC>[CH3:11][O:10][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([O:8][CH3:9])[C:2]=1[C:22](=[O:24])[CH2:23][C:18]([CH3:17])([CH3:26])[CH2:19][C:20]([O:21][CH3:12])=[O:25]

Participants

14

Reactant 7

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 778133,3-Dimethylglutaric anhydrideHCID 113914072-Iodo-1,3-dimethoxybenzeneHCID 178418918HCID 178418918, compound

Product 1

HCID 69083859HCID 69083859, compound

Reagents, catalysts & solvents 6

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

A cooled (−10° C.) solution of commercially available 2-iodo-1,3-dimethoxybenzene (2.000 g; 7.57 mmol) in anh. THF (30 ml) was treated dropwise with a solution of 2 M isopropylmagnesium chloride in THF (5.10 ml; 10.20 mmol), and the mixture was further stirred at −10° C., under nitrogen, for 15 min. This mixture was then added dropwise to a cooled (−40° C.) solution of commercially available 4,4-dimethyldihydro-2H-pyran-2,6(3H)-dione (1.184 g; 8.33 mmol) and CuI (360 mg; 1.89 mmol) in anh. THF (20 ml). Stirring was continued at −40° C. for 20 min., and 2 M aq. HCl (11.5 ml) was then added dropwise. Et2O (100 ml), and aq. sat. NH4Cl (30 ml) were added, and the separated organic layer was dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Anh. DMF (20 ml), and Cs2CO3 (3.080 g; 9.45 mmol) were successively added, and stirring at rt was continued for 15 min. After cooling to 0° C., iodomethane (1.610 g; 11.34 mmol) was added dropwise, and the resulting mixture was further stirred at 0° C. for 10 min., and then at rt for 1.5 h. AcOEt (100 ml) and water (100 ml) were added, and the separated organic layer was further washed with brine (25 ml), dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=20/1) afforded methyl 5-(2,6-dimethoxyphenyl)-3,3-dimethyl-5-oxopentanoate as a yellow oil. LC-MS (conditions D): tR=1.01 min.; [M+H]+: 295.39 g/mol.

Workup

  1. additionThis mixture was then added dropwise to
  2. stirringStirring
  3. waitwas continued at −40° C. for 20 min.
  4. dry with materialthe separated organic layer was dried over anh. MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. stirringstirring at rt
  8. waitwas continued for 15 min
  9. temperatureAfter cooling to 0° C.
  10. stirringthe resulting mixture was further stirred at 0° C. for 10 min.
  11. waitat rt for 1.5 h
  12. washthe separated organic layer was further washed with brine (25 ml)
  13. dry with materialdried over anh. MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated to dryness under reduced pressure
  16. customPurification by FC (DCM/MeOH=20/1)

Sources & evidence

ORD record
ord-21716418ad5442ccb4d62f2205e36ad8
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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