Acetic Anhydride → N-[4-methyl-3-(2-phenoxy-ethoxy)-phenyl]-acetamide

HRID 330783Notes

Reaction equation

HRID 330783 reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].[NH2:8][C:9]1[CH:10]=[CH:11][C:12]([CH3:16])=[C:13]([OH:15])[CH:14]=1.Br[C:18]1[CH:19]=[C:20]([O:24][CH2:25][CH3:26])[CH:21]=[CH:22][CH:23]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C(O)(=O)C.CN(C=O)C.O>[CH3:16][C:12]1[CH:11]=[CH:10][C:9]([NH:8][C:1](=[O:3])[CH3:2])=[CH:14][C:13]=1[O:15][CH2:26][CH2:25][O:24][C:20]1[CH:21]=[CH:22][CH:23]=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 7918Acetic AnhydrideHCID 10796Cesium carbonateHCID 178185-Amino-2-methylphenolHCID 758673-Bromophenetole

Product 1

HCID 86684778N-[4-methyl-3-(2-phenoxy-ethoxy)-phenyl]-acetamide

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Acetic anhydride (1.25 mL, 12.2 mmol) was added to a solution of 5-amino-2-methyl phenol (1.0 g, 8.1 mmol) in acetic acid (6 mL), and the reaction was refluxed for 5 mins. Then the reaction mixture was cooled to room temperature and the product was solidified. It was filtered off and washed with water (4 mL) and dried to obtain the product along with the trace amount of O-acylated product. The mixture, to which was added 3-bromophenetole (1.33 g, 6.6 mmol) and Cs2CO3 (2.927 g, 9.0 mmol) in DMF (10 mL), was stirred overnight at 50° C. The reaction mixture was then diluted with water (10 mL) and extracted with ethyl acetate (3×20 mL). The combined extracts were dried over sodium sulfate and recrystallized from toluene to obtain the pure product 18a in 65% (yield over two steps) as an off-white solid.

Workup

  1. temperaturethe reaction was refluxed for 5 mins
  2. filtrationIt was filtered off
  3. washwashed with water (4 mL)
  4. customdried
  5. customto obtain the product along with the trace amount of O-acylated product
  6. extractionextracted with ethyl acetate (3×20 mL)
  7. dry with materialThe combined extracts were dried over sodium sulfate
  8. customrecrystallized from toluene

Sources & evidence

ORD record
ord-904dd1e5c9634532a7bdbe92ef1dfa80
Source dataset
uspto-grants-2014_11
Patent number
US08877752B2

Reaction notes

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