N-Methoxy-N-methyl-2-(2-methylphenyl)acetamide → 1-(2-Methylphenyl)propan-2-one

HRID 706381Notes

Reaction equation

HRID 706381 reaction equation
[CH3:1][Mg]Cl.CON(C)[C:7](=[O:16])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH3:15]>C1COCC1>[C:10]1([CH3:15])[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[CH2:8][C:7](=[O:16])[CH3:1]

Participants

4

Reactant 2

HCID 21099310N-Methoxy-N-methyl-2-(2-methylphenyl)acetamideHCID 178418332HCID 178418332, compound

Product 1

HCID 27341091-(2-Methylphenyl)propan-2-oneYield 81.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
47.5 °C

Procedure

A solution of CeCl3 (114.4 g, 0.45 mol) in THF (4 L) was degassed for 1 h and heated to 45-50° C. for 5 h. When the solution was cooled to −10˜−5° C., MeMgCl (193.2 g, 2.6 mol) in THF was added and the mixture was stirred for 1 h at −10˜−5° C. After amide 34 (256 g, 1.3 mol) was charged into the reaction mixture at −10˜−5° C., the mixture was stirred for 5 h at 10-20° C. After the reaction was complete monitored by LCMS, the mixture was quenched by 1M HCl, and then partitioned with water and EtOAc. The organic phase was dried over Na2SO4 and concentrated. The crude residual was further purified by flash chromatography on silica gel (2-10% EtOAc/PE) to give 35 (157 g, 80% yield). 1H NMR (CDCl3, 400 MHz): δ 7.1-6.91 (d, 4H), 3.55 (s, 3H), 2.25 (s, 3H), 2.05 (s, 3H); MS (ESI) m/e [M+H]+: 149.05.

Workup

  1. temperatureWhen the solution was cooled to −10˜−5° C.
  2. stirringthe mixture was stirred for 5 h at 10-20° C
  3. customthe mixture was quenched by 1M HCl
  4. custompartitioned with water and EtOAc
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude residual was further purified by flash chromatography on silica gel (2-10% EtOAc/PE)

Sources & evidence

ORD record
ord-f9763f3807e246008052abc54f36420c
Source dataset
uspto-grants-2015_11
Patent number
US09174989B2

Reaction notes

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