Acetic Acid → 3-(3-Acetamidophenyl)prop-2-enoic acid

HRID 2405748Notes

Reaction equation

HRID 2405748 reaction equation
C([O:4][C:5](=[O:7])[CH3:6])(=O)C.[C:8]([NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(=[O:10])[CH3:9].O.[C:19](O)(=O)C>>[C:8]([NH:11][C:12]1[CH:17]=[C:16]([CH:15]=[CH:14][CH:13]=1)[CH:19]=[CH:6][C:5]([OH:4])=[O:7])(=[O:10])[CH3:9]

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 904AcetanilideHCID 962WaterHCID 7918Acetic Anhydride

Product 1

HCID 534395323-(3-Acetamidophenyl)prop-2-enoic acidYield 89%

Procedure

Tin II chloride dihydrate (170 g, 0.75 mol) was dissolved in concentrated HCl (200 mL). Warming was necessary to obtain a clear solution. 3-Nitrocinnamic acid (35 g, 0.181 mol) was added portionwise with stirring. After about 20% of the 3-nitrocinnamic acid had been added, the mixture was warmed with a heat gun to 45° C. to initiate reaction. The rate of addition was controlled to maintain a temperature of 65-75° C. The reaction was exothermic, but not vigorous on this scale. After the addition was complete, and the reaction started to subside, the flask was transferred to an oil bath at 65° C. for 1 h. The mixture was then cooled to room temperature. The solid was filtered, washed with 2 N HCl, (100 mL) and sucked dry. The filter cake was dried in a vacuum oven for 1 h, then in air overnight, to give about 65 g of the crude amine. This material was suspended in acetic acid (300 mL) and acetic anhydride (150 mL, 1.6 mol) was added gradually with stirring. After the initial exotherm subsided, the mixture was stirred in an oil bath at 110° C. for 2 h, resulting in a clear solution. LCMS showed complete conversion to the desired acetanilide. The solution was cooled and water (50 mL) was added. After standing overnight the solution was concentrated to about 300 mL. More water (100 mL) and 2 N HCl (50 mL) were added. The precipitate was filtered, washed with water and dried to give 3-acetamido cinnamic acid (33.2 g, 89%).

Workup

  1. stirringthe mixture was stirred in an oil bath at 110° C. for 2 h
  2. customresulting in a clear solution
  3. temperatureThe solution was cooled
  4. concentrationthe solution was concentrated to about 300 mL
  5. additionMore water (100 mL) and 2 N HCl (50 mL) were added
  6. filtrationThe precipitate was filtered
  7. washwashed with water
  8. customdried

Sources & evidence

ORD record
ord-90c87f096d7f44d388489833ef19e4d0
Source dataset
uspto-grants-2014_08
Patent number
US08809326B2

Reaction notes

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