Methyl chloroformate → HCID 58515775, compound

HRID 1191591Notes

Reaction equation

HRID 1191591 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:20][CH3:21])=[C:6]([CH:8]2[C:13](=[O:14])[C:12]([CH3:16])([CH3:15])[O:11][C:10]([CH3:18])([CH3:17])[C:9]2=[O:19])[CH:7]=1.[Cl:22][C:23]1[CH:24]=[N:25][NH:26][CH:27]=1.N1CCC[C@H]1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(N(CC)CC)C.Cl[C:52]([O:54][CH3:55])=[O:53]>[Cu]I>[CH3:55][O:54][C:52](=[O:53])[O:19][C:9]1[C:10]([CH3:18])([CH3:17])[O:11][C:12]([CH3:16])([CH3:15])[C:13](=[O:14])[C:8]=1[C:6]1[CH:7]=[C:2]([N:25]2[CH:24]=[C:23]([Cl:22])[CH:27]=[N:26]2)[CH:3]=[CH:4][C:5]=1[CH2:20][CH3:21]

Participants

8

Reactant 6

HCID 6586Methyl chloroformateHCID 8471TriethylamineHCID 275241H-Pyrazole, 4-chloro-HCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 666785694-(5-Bromo-2-ethylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione

Product 1

HCID 58515775HCID 58515775, compoundYield 41.3%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
160 °C

Procedure

To a mixture of 4-(5-bromo-2-ethylphenyl)-2,2,6,6-tetramethylpyran-3,5-dione (0.15 g, 0.42 mmol), 4-chloropyrazole (0.065 g, 0.63 mmol), L-proline (0.049 g, 0.42 mmol), copper(I) iodide (0.080 g, 0.42 mmol) and anhydrous powdered potassium phosphate (0.36 g, 1.68 mmol) is added degassed anhydrous dimethylsulfoxide (1.5 ml). This mixture is then heated at 160° C. under microwave irradiation for 30 minutes, followed by cooling to room temperature, dilution with dichloromethane (150 ml) and washing with 1M aqueous hydrochloric acid (2×50 ml). The organic fractions are combined, dried over anhydrous magnesium sulfate, then concentrated in vacuo. Diethyl ether is then added to the crude oil to precipitate the product, which is filtered and re-dissolved in dichloromethane (20 ml). To this solution is then added triethylamine (0.16 ml, 1.16 mmol) followed by methyl chloroformate (0.090 ml, 1.16 mmol) and stirring at room temperature for 3 hours. The solvents are removed under reduced pressure, and the residue is purified directly by column chromatography on silica gel (hexane/ethyl acetate 3:1 ratio) to afford carbonic acid 4-[5-(4-chloropyrazol-1-yl)-2-ethylphenyl]-2,2,6,6-tetramethyl-5-oxo-5,6-dihydro-2H-pyran-3-yl ester methyl ester (0.075 g) as a colourless oil.

Workup

  1. additionis added
  2. customdegassed anhydrous dimethylsulfoxide (1.5 ml)
  3. temperatureby cooling to room temperature
  4. washdilution with dichloromethane (150 ml) and washing with 1M aqueous hydrochloric acid (2×50 ml)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. additionDiethyl ether is then added to the crude oil
  8. customto precipitate the product, which
  9. filtrationis filtered
  10. dissolutionre-dissolved in dichloromethane (20 ml)
  11. customThe solvents are removed under reduced pressure
  12. customthe residue is purified directly by column chromatography on silica gel (hexane/ethyl acetate 3:1 ratio)

Sources & evidence

ORD record
ord-b5c50094947b41a28523f10501374e3a
Source dataset
uspto-grants-2014_03
Patent number
US08680012B2

Reaction notes

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