Acetic Anhydride → Methyl 4-acetamidosalicylate

HRID 1018790Notes

Reaction equation

HRID 1018790 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([OH:12])[C:5](=[CH:10][CH:11]=1)[C:6]([O:8][CH3:9])=[O:7].[C:13](OC(=O)C)(=[O:15])[CH3:14]>O>[C:13]([NH:1][C:2]1[CH:3]=[C:4]([OH:12])[C:5](=[CH:10][CH:11]=1)[C:6]([O:8][CH3:9])=[O:7])(=[O:15])[CH3:14]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 77787Methyl p-aminosalicylate

Product 1

HCID 77719Methyl 4-acetamidosalicylateYield 70%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a suspension of 4.17 g (0.025 mole) methyl 4-aminosalicylate (9) in 20 mL water, was added 3 mL (0.032 mole) acetic anhydride (Aldrich 11,004-3) while stirring. The mixture was heated at 800 for 30 minutes and cooled to room temperature. The precipitate was collected and added into 100 ml of 10% hydrochloric acid. This suspension was stirred at room temperature for 10 minutes, filtered and dried to give 4.3 g (82%) of a crude solid, which was recrystallized from H2O/CH3OH, yielding 3 g (70%) of 10 as white crystals, mp 153-154 . Infrared (IR) and NMR analysis gave the following results: IR (potassium bromide): 3319(NH), 1680 (C=O),1604, 1157 cm−1. 1H nmr (90 MHz, CDCI3 +DMSO-d6):δ 10.80 (1H, S, OH), 9.74 (1H, br s, NH), 7.73 (1H; d, 3JH5-H6=9 Hz; H-6), 7.37 (1H; d, 4JH5-H3=1.8 Hz; H-3),7.11 (1H; dd, 3JH6-H5=9HZ, 4JH3-H5=1.8 Hz; H-5), 3.91 (3H; s; OCH3), 2.15 (3H, s, CH3).

Workup

  1. temperatureThe mixture was heated at 800 for 30 minutes
  2. customThe precipitate was collected
  3. additionadded into 100 ml of 10% hydrochloric acid
  4. stirringThis suspension was stirred at room temperature for 10 minutes
  5. filtrationfiltered
  6. customdried
  7. customto give 4.3 g (82%) of a crude solid, which
  8. customwas recrystallized from H2O/CH3OH

Sources & evidence

ORD record
ord-7cac015490ce4e4b8284a17cbf06fb6f
Source dataset
uspto-grants-2002_11
Patent number
US06482982B1

Reaction notes

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