Diethylcarbamoyl chloride → 2-isopropyl-4-methoxy-N,N-diethylbenzamide

HRID 1957428Notes

Reaction equation

HRID 1957428 reaction equation
[CH:1]([C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1Br)([CH3:3])[CH3:2].C([Li])CCC.[CH2:18]([N:20]([CH2:24][CH3:25])[C:21](Cl)=[O:22])[CH3:19]>C(OCC)C>[CH:1]([C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[C:21]([N:20]([CH2:24][CH3:25])[CH2:18][CH3:19])=[O:22])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6916Diethylcarbamoyl chlorideHCID 117464064-Bromo-3-isopropylanisoleHCID 178418339Butyllithium

Product 1

HCID 102643402-isopropyl-4-methoxy-N,N-diethylbenzamideYield 79.3%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of 40.0 g (0.174 mol) of 2-isopropyl-4-methoxybromobenzene in 600 ml of diethyl ether at 0° C. was added 103.68 ml (0.175 mol) of a 1.69M solution of butyl lithium in diethyl ether. When the addition was complete the solution was cooled to 0° C. for one hour and stirred for an additional five hours at ambient temperature, then recooled to -78° C. and treated with a solution of 23.68 g (0.175 mol) of N,N-diethylcarbamyl chloride in 80 ml of diethyl ether. The resulting solution was stirred for about 12 hours while the reaction temperature was allowed to rise and then quenched with saturated ammonium chloride solution. The aqueous and organic layers were separated, the aqueous layer back extracted with ethyl acetate and the combined organic extracts washed once with brine, then dried and the solution taken to dryness to give a crude product which was flash chromatographed on silica gel, eluting with 30% ethyl acetate/hexane to give 34.4 g (79%) of 2-isopropyl-4-methoxy-N,N-diethylbenzamide as an oil which was used as such in the next step without further purification. The oil can be distilled, if desired, and boils at 123-129/0.2-0.3 mm.

Workup

  1. additionWhen the addition
  2. customrecooled to -78° C.
  3. stirringThe resulting solution was stirred for about 12 hours while the reaction temperature
  4. customquenched with saturated ammonium chloride solution
  5. customThe aqueous and organic layers were separated
  6. extractionthe aqueous layer back extracted with ethyl acetate
  7. washthe combined organic extracts washed once with brine
  8. customdried
  9. customto give a crude product which
  10. customchromatographed on silica gel
  11. washeluting with 30% ethyl acetate/hexane

Sources & evidence

ORD record
ord-16739339983b495cb69abf08a9159d2e
Source dataset
uspto-grants-1998_07
Patent number
US05783589

Reaction notes

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