Methyl iodide → [4-(Cyclopropylcarbonyl)phenyl]methyl-propanedioic acid, diethyl ester

HRID 1838689Notes

Reaction equation

HRID 1838689 reaction equation
[CH:1]1([C:4]([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][C:13](OCC)=O)=[CH:8][CH:7]=2)=[O:5])[CH2:3][CH2:2]1.C(O[C:21](=[O:25])[O:22][CH2:23][CH3:24])C.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:21]([O:22][CH2:23][CH3:24])=[O:25])[C:21]([O:22][CH2:23][CH3:24])=[O:25])=[CH:10][CH:11]=2)=[O:5])[CH2:2][CH2:3]1

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 7766Diethyl CarbonateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 11218514Ethyl 2-(4-(cyclopropanecarbonyl)phenyl)acetate

Product 1

HCID 12132442[4-(Cyclopropylcarbonyl)phenyl]methyl-propanedioic acid, diethyl esterYield 26.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Dissolve 4-(cyclopropylcarbonyl)benzeneacetic acid, ethyl ester (6.5 g, 28 mmol) and diethylcarbonate (4.0 g, 34 mmol) in tetrahydrofuran (100 mL). Add 62 mL (62 mmol) of a 1.0 molar solution of sodium bis(trimethylsilyl)amide in tetrahydrofuran over 0.5 hours. Stir 28 hours. Add iodomethane (5.3 g, 35 mmol). Stir 2 days. Add water and ethyl acetate. Wash organic phase with brine, dry over anhydrous magnesium sulfate and concentrate. Purify by flash chromatography (200 g silica gel, ethyl acetate/heptane as eluent) to give the title compound (1.43 g, 17%).

Workup

  1. stirringStir 2 days
  2. dry with materialWash organic phase with brine, dry over anhydrous magnesium sulfate
  3. concentrationconcentrate
  4. customPurify by flash chromatography (200 g silica gel, ethyl acetate/heptane as eluent)

Sources & evidence

ORD record
ord-7aceff524a2b405888b96be3d0c79ba1
Source dataset
uspto-grants-2004_01
Patent number
US06673933B2

Reaction notes

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