Methyl iodide → [4-(Cyclopropylcarbonyl)pheny]methyl-propanedioic acid, dimethyl ester

HRID 2120386Notes

Reaction equation

HRID 2120386 reaction equation
[CH:1]1([C:4]([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][C:13](OC)=O)=[CH:8][CH:7]=2)=[O:5])[CH2:3][CH2:2]1.CO[C:19](=[O:22])[O:20][CH3:21].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].IC>O1CCCC1.C(OCC)(=O)C.O>[CH:1]1([C:4]([C:6]2[CH:7]=[CH:8][C:9]([CH2:12][CH:13]([C:19]([O:20][CH3:21])=[O:22])[C:19]([O:20][CH3:21])=[O:22])=[CH:10][CH:11]=2)=[O:5])[CH2:2][CH2:3]1

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 12021Dimethyl CarbonateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 12096482Methyl 2-(4-(cyclopropanecarbonyl)phenyl)acetate

Product 1

HCID 67524057[4-(Cyclopropylcarbonyl)pheny]methyl-propanedioic acid, dimethyl esterYield 21.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Dissolve 4-(cyclopropylcarbonyl)benzeneacetic acid, methyl ester (1.5 g, 6.0 mmol) and dimethylcarbonate (930 mg, 10.3 mmol) in tetrahydrofuran (10 mL). Add 20 mL (20 mmol) of a 1.0 molar solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran over 0.5 hours. Stir 3 days. Add iodomethane (5.3 g, 35 mmol). Stir 24 hours. Add water and ethyl acetate. Wash organic phase with brine, dry over anhydrous magnesium sulfate and concentrate. Purify by flash chromatography (50 g silica gel, ethyl acetate/heptane as eluent) to give the title compound (315 mg, 16%). Additionally, the following compounds can be prepared by the synthetic procedure depicted in Step F:

Workup

  1. stirringStir 24 hours
  2. dry with materialWash organic phase with brine, dry over anhydrous magnesium sulfate
  3. concentrationconcentrate
  4. customPurify by flash chromatography (50 g silica gel, ethyl acetate/heptane as eluent)

Sources & evidence

ORD record
ord-56c74f848b644e8da24506c7ecb7536d
Source dataset
uspto-grants-2004_02
Patent number
US06689898B2

Reaction notes

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