Methyl 2-methyl-4-oxo-4H-1-benzopyran-3-carboxylate → Methyl 2-(3,4-dichlorophenyl)-2-methyl-4-oxochroman-3-carboxylate

HRID 409513Notes

Reaction equation

HRID 409513 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([Mg]Br)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:11][C:12]1[O:13][C:14]2[C:19]([C:20](=[O:26])[C:21]=1[C:22]([O:24][CH3:25])=[O:23])=[CH:18][CH:17]=[CH:16][CH:15]=2>O1CCCC1.[Cu]Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2([CH3:11])[CH:21]([C:22]([O:24][CH3:25])=[O:23])[C:20](=[O:26])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[O:13]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 2

HCID 332660Methyl 2-methyl-4-oxo-4H-1-benzopyran-3-carboxylateHCID 178478192HCID 178478192, compound

Product 1

HCID 67155925Methyl 2-(3,4-dichlorophenyl)-2-methyl-4-oxochroman-3-carboxylateYield 62%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

A suspension of copper(I) chloride (454 mg, 4.58 mmol) in tetrahydrofuran (5.0 mL) was stirred in a dry flask under nitrogen on ice. A solution of (3,4-dichlorophenyl)magnesium bromide (0.5 M) in THF (9.17 mL, 4.58 mmol) was added over about a 2 min. period. The resulting mixture was stirred on ice for 5 min, and then treated with a solution of methyl 2-methyl-4-oxo-4H-chromene-3-carboxylate (500 mg, 2.29 mmol) in THF (6.0 mL) over about a 2 min. period. The mixture was stirred on ice for 10 min, and then allowed to warm to rt. After 4.5 h at rt, the reaction mixture was quenched by adding 9:1 saturated aqueous ammonium chloride/aqueous ammonia (20 mL). Upon completion of addition, the reaction mixture was stirred at rt for 10 min. and then ethyl acetate and additional ammonium chloride were added. The aqueous and organic layers were mixed well and then separated. The organic layer was washed twice with saturated ammonium chloride, dried over sodium sulfate and then concentrated under vacuum to yield a residue. The residue was purified by column chromatography (silica gel, 9:1 hexane-ethyl acetate) to provide methyl 2-(3,4-dichlorophenyl)-2-methyl-4-oxochroman-3-carboxylate as a colorless gum (518 mg, 62%). By NMR, this material was mixture of the enol form and 2 diastereomeric keto forms (ratio about 1:1:2). Mass spectrum m/z 387.01, 389.03 (M+Na)+.

Workup

  1. stirringThe resulting mixture was stirred on ice for 5 min
  2. stirringThe mixture was stirred on ice for 10 min
  3. customthe reaction mixture was quenched
  4. additionby adding 9:1 saturated aqueous ammonium chloride/aqueous ammonia (20 mL)
  5. additionUpon completion of addition
  6. stirringthe reaction mixture was stirred at rt for 10 min.
  7. additionethyl acetate and additional ammonium chloride were added
  8. additionThe aqueous and organic layers were mixed well
  9. customseparated
  10. washThe organic layer was washed twice with saturated ammonium chloride
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated under vacuum
  13. customto yield a residue
  14. customThe residue was purified by column chromatography (silica gel, 9:1 hexane-ethyl acetate)

Sources & evidence

ORD record
ord-2cd40653ac644ed3a21b0bef928856f8
Source dataset
uspto-grants-2014_06
Patent number
US08759390B2

Reaction notes

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