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

HRID 2092392Notes

Reaction equation

HRID 2092392 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:16]I.[NH4+].[Cl-]>CN(C=O)C>[CH2:12]([O:11][C:9](=[O:10])[CH:8]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=1)[CH3:16])[CH3:13]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 7020609Ethyl 2-(4-bromophenyl)acetate

Product 1

HCID 13840376Ethyl 2-(4-bromophenyl)propanoateYield 37%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 4-bromophenylacetate (2 g, 8.23 mmol) in anhydrous DMF (20 ml) was carefully added NaH (60% in mineral oil, 0.494 g, 12.34 mmol) at 0° C. (ice bath). The resulting slurry was stirred at 0° C. for 30 min, then MeI (0.643 ml, 10.28 mmol) was added and the reaction mixture was allowed to warm to RT and further stirred for 1 h. A saturated aqueous NH4Cl solution was added to quench the reaction and the mixture was extracted with AcOEt (2×). The combined organic fractions were dried over Na2SO4, filtered and evaporated to dryness. The resulting crude material was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, heptane/AcOEt 99:1 to 8:2) to yield the title compound (777.8 mg, 3.03 mmol, 37% yield) as a colorless oil. TLC: RF=0.64 (heptane/AcOEt 3:1); HPLC: AtRet=2.60 min; 1H NMR (400 MHz, DMSO-d6): 1.13 (t, J=7.1, 3H), 1.37 (d, J=7.1, 3H), 3.79 (q, J=7.1, 1H), 3.98-4.12 (m, 2H), 7.22-7.28 (m, 2H), 7.49-7.56 (m, 2H).

Workup

  1. customat 0° C.
  2. temperatureto warm to RT
  3. stirringfurther stirred for 1 h
  4. customto quench
  5. customthe reaction
  6. extractionthe mixture was extracted with AcOEt (2×)
  7. dry with materialThe combined organic fractions were dried over Na2SO4
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customThe resulting crude material was purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, heptane/AcOEt 99:1 to 8:2)

Sources & evidence

ORD record
ord-3d143dd021254c198abf97f8d745cc24
Source dataset
uspto-grants-2013_05
Patent number
US08440693B2

Reaction notes

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