Methanol → 1-[(4-Ethoxybenzoyl)amino]cyclopropanecarboxylic acid
Reaction equation
[CH2:1]([O:3][C:4]1[CH:20]=[CH:19][C:7]([C:8]([NH:10][C:11]2([C:14]([O:16]CC)=[O:15])[CH2:13][CH2:12]2)=[O:9])=[CH:6][CH:5]=1)[CH3:2].C1COCC1.CO>O>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]([C:8]([NH:10][C:11]2([C:14]([OH:16])=[O:15])[CH2:12][CH2:13]2)=[O:9])=[CH:19][CH:20]=1)[CH3:2]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 20 °C
Procedure
Charge an 800 L reactor with ethyl 1-[(4-ethoxybenzoyl)amino]cyclopropanecarboxylate (12.19 kg), THF (45.5 kg) and MeOH (20.2 kg). Add a solution of LiOH monohydrate (2.49 kg) in water (25.6 kg) to the reactor maintaining the temperature of less than 23° C. during the transfer. Stir the resulting solution at 20±3° C. for overnight (19 h). Remove THF and MeOH by vacuum distillation and then add water (67 kg) to reactor. Adjust the pH of the reaction to pH about 2.0 with 5N HCl (about 12 L) at 17±2° C. Stir the resulting product slurry at 17±2° C. for 50 minutes. Collect the solids by filtration and wash with water (3×40 Kg). Dry the wet cake at 47° C. under vacuum to afford 1-[(4-ethoxybenzoyl)amino]cyclopropanecarboxylic acid (10.74 kg, 98% yield, >99% purity by HPLC, 0.03% KF) as a white powder solid. LC-MS (M+1=250).
Workup
- temperaturemaintaining the temperature of less than 23° C. during the transfer
- distillationRemove THF and MeOH by vacuum distillation
- customthe pH of the reaction to pH about 2.0 with 5N HCl (about 12 L) at 17±2° C
- stirringStir the resulting product slurry at 17±2° C. for 50 minutes
- customCollect the solids
- filtrationby filtration
- washwash with water (3×40 Kg)
- customDry the wet cake at 47° C. under vacuum
Sources & evidence
- ORD record
- ord-e1b51a8a43b54c77b665aa857bff0879
- Source dataset
- uspto-grants-2012_10
- Patent number
- US08299061B2
Reaction notes
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