Methyl iodide → Ethyl 2-(4-methylphenyl)propanoate

HRID 47979

Reaction equation

HRID 47979 reaction equation
[C:1]1([CH3:13])[CH:6]=[CH:5][C:4]([CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9])=[CH:3][CH:2]=1.[Li+].[CH3:15]C([N-]C(C)C)C.CI.CN1C(=O)N(C)CCC1>C1COCC1.O>[CH2:11]([O:10][C:8](=[O:9])[CH:7]([C:4]1[CH:3]=[CH:2][C:1]([CH3:13])=[CH:6][CH:5]=1)[CH3:15])[CH3:12]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 84175Ethyl p-tolylacetateHCID 2724682Lithium diisopropylamide

Product 1

HCID 11070524Ethyl 2-(4-methylphenyl)propanoateYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under N2 atmosphere, a solution of ethyl p-tolyl-acetate (2.72 g, 15.2 mmol) in anhydrous THF (70 mL) was cooled to −40° C. and a solution of LDA (7.6 mL, 15.25 mmol) was added drop-wise over 30 minutes. The reaction mixture was stirred for 1 h, and methyl iodide (3.03 g, 21.30 mmol) was added drop-wise, followed by the addition of DMPU (1 mL). The reaction mixture was allowed to warm to rt, after 1 h and stirred overnight. The reaction mixture was poured into water (30 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with saturated NH4Cl solution (10 mL), 1 M HCl (10 mL), saturated NaHCO3 solution (10 mL), and brine (10 mL), then dried over MgSO4, and concentrated in vacuo. The residue was distilled in high vacuo (bp. 59-63° C./0.2 mmHg) to furnish 2-p-tolyl-propionic acid ethyl ester (2.5 g, 86.0%) as an oil. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm) 7.18 (d, 2H, J=8.1), 7.10 (d, 2H, J=8.1), 4.09 (m, 2H), 3.67 (q, 1H, J=7.2), 2.29 (s, 3H), 1.47 (d, J=7.2 Hz, 3H), 1.20 (t, J=5.7 Hz, 3H). 13C NMR (75 MHz, CDCl3/TMS): δ (ppm) 174.71, 137.80, 136.63, 129.33, 129.14, 127.36, 60.66, 45.18, 21.05, 18.70, 14.15. [Lit. ref.: Ghosh, S.; Pardo, S. N.; Salomon, R. G. J. Org. Chem. 1982, 47, 4692-4702.].

Workup

  1. stirringstirred overnight
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. washThe combined organic layers were washed with saturated NH4Cl solution (10 mL), 1 M HCl (10 mL), saturated NaHCO3 solution (10 mL), and brine (10 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. distillationThe residue was distilled in high vacuo (bp. 59-63° C./0.2 mmHg)

Sources & evidence

ORD record
ord-ca9def63100b4ddebf5000a311a509bf
Source dataset
uspto-grants-2004_03
Patent number
US06699910B2

Linked notes

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