Acetic Anhydride → Benzoic acid, 4-(acetyloxy)-3-methoxy-
Reaction equation
[C:1](OC(=O)C)(=[O:3])[CH3:2].[OH:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][C:10]=1[O:18][CH3:19]>>[C:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][C:10]=1[O:18][CH3:19])(=[O:3])[CH3:2]Participants
Procedure
Acetic anhydride (72.9 g, 67.4 mL) is added under nitrogen at room temperature to 4-hydroxy-3-methoxybenzoic acid (97.7 g) in xylenes (817 g, 950 mL) while stirring. The stirred mixture is heated to 115°-125° C. and heated at 120°-125° C. for 4 to 20 hours under nitrogen. Part of the liquid is then removed by distillation at about 150° bath temperature to a volume of about 700 ml and the mixture is cooled to room temperature to obtain a slurry of 4-acetoxy-3-methoxybenzoic acid which is again diluted with additional xylenes (224 g, 226 mL). N,N-dimethylformamide (DMF, 1.9 g, 2.0 mL) is added followed by dropwise addition, over 2.5 hours, of oxalyl chloride (90.6 g, 62.2 mL). The reaction mixture is stirred at room temperature for 24 hours to obtain a solution of 4-acetoxy-3-methoxybenzoyl chloride which is used as such in the next step. The xylenes solution is cooled to -14° to -20° C. with a brine solution and diisopropylamine (169 g, 234 mL) is added dropwise over a 45 minute period, at a rate so that the temperature does not exceed 0° C. The reaction mixture is allowed to warm to room temperature and is stirred at room temperatue (17°-20° C.) for 21 hours. The resulting slurry is filtered under vacuum, and the filter cake is further slurried with xylenes (430 mL) and filtered.
Workup
- temperatureThe stirred mixture is heated to 115°-125° C.
- temperatureheated at 120°-125° C. for 4 to 20 hours under nitrogen
- customPart of the liquid is then removed by distillation at about 150° bath temperature to a volume of about 700 ml
Sources & evidence
- ORD record
- ord-fe10e27ce1d94b029aaf1e48f94e2ffd
- Source dataset
- uspto-grants-1996_01
- Patent number
- US05488160
Reaction notes
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