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N-Methoxy-N-methyl-2-(2,3,5-trifluorophenyl)acetamide → 1-(2,3,5-Trifluorophenyl)propan-2-one

HRID 706388
Notes
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Reaction equation

HRID 706388 reaction equation
[CH3:1][Mg]Cl.CON(C)[C:7](=[O:18])[CH2:8][C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[C:11]([F:16])[C:10]=1[F:17]>C1COCC1>[F:17][C:10]1[C:11]([F:16])=[CH:12][C:13]([F:15])=[CH:14][C:9]=1[CH2:8][C:7](=[O:18])[CH3:1]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 89814700N-Methoxy-N-methyl-2-(2,3,5-trifluorophenyl)acetamideHCID 178418332HCID 178418332, compound

Product 1

HCID 552746081-(2,3,5-Trifluorophenyl)propan-2-oneYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
47.5 °C

Procedure

A solution of CeCl3 (11.44 g, 0.045 mol) in THF (350 mL) was degassed for 1 h and heated to 45-50° C. for 5 h. When the solution was cooled to −10-5° C., MeMgCl (19.44 g, 0.26 mol) in THF was added and the mixture was stirred for 1 h at −10-5° C. After amide 43 (30.3 g, 0.13 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, 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 44 (20.8 g, 85% yield). 1H NMR (CDCl3, 400 MHz): δ 6.91-6.78 (m, 1H), 6.69 (dd, 1H), 3.77 (d, 2H), 2.25 (s, 3H); MS (ESI) m/e [M+H]+: 189.05.

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-f8e8e89dc2444a0abc36b5775342f180
Source dataset
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09174989B2

Reaction notes

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