Methyl iodide → 2,2-Bis-(4-chloro-phenyl)-propionic acid methyl ester

HRID 45553Notes

Reaction equation

HRID 45553 reaction equation
[CH3:1][O:2][C:3](=[O:19])[CH:4]([C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)[C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][CH:6]=1.[Li+].[CH3:21]C([N-]C(C)C)C.IC>C1COCC1>[CH3:1][O:2][C:3](=[O:19])[C:4]([C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)([C:5]1[CH:6]=[CH:7][C:8]([Cl:11])=[CH:9][CH:10]=1)[CH3:21]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 346996Methyl bis(p-chlorophenyl)acetateHCID 2724682Lithium diisopropylamide

Product 1

HCID 235629742,2-Bis-(4-chloro-phenyl)-propionic acid methyl esterYield 17%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of bis-(4-chloro-phenyl)-acetic acid methyl ester (1.19 g, 4.0 mmol) in THF (20 ml) was cooled to −78° C. under nitrogen. A solution of LDA (3.0 mL, 6.0 mmol, 2M in heptane/THF/ethylbenzene) was added over 5 minutes, then after a further 20 minutes, iodomethane (0.63 ml, 10.1 mmol) was added. After 4 hours the reaction was quenched by the addition of saturated ammonium chloride solution and allowed to warm to room temperature then concentrated in vacuo to remove organic solvents. The mixture was diluted with ethyl acetate/petrol 1:4 and washed with saturated ammonium chloride solution then brine, dried (MgSO4), filtered and concentrated to give a residue which was purified by column chromatography (SiO2), eluting with an ethyl acetate/petrol gradient (1% to 2%), to afford the title compound as a colourless oil (210 mg, 17%); LCMS (PS-B3) Rt 4.01 min, No ionisation. 1H NMR (CDCl3) δ 1.88 (3H, s), 3.73 (3H, 5), 7.11-7.14 (4H, m), 7.26-7.30 (4H, m).

Workup

  1. customAfter 4 hours the reaction was quenched by the addition of saturated ammonium chloride solution
  2. concentrationthen concentrated in vacuo
  3. customto remove organic solvents
  4. additionThe mixture was diluted with ethyl acetate/petrol 1:4
  5. washwashed with saturated ammonium chloride solution
  6. dry with materialbrine, dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a residue which
  10. customwas purified by column chromatography (SiO2)
  11. washeluting with an ethyl acetate/petrol gradient (1% to 2%)

Sources & evidence

ORD record
ord-174f182de0264f5cb49dc6322445dab2
Source dataset
uspto-grants-2013_09
Patent number
US08541461B2

Reaction notes

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