Hydrochloric Acid → 4-Fluoro-alpha-[(phenylmethyl)amino]benzeneacetic acid methyl ester hydrochloride
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[ClH:20].[CH3:21]O>>[ClH:20].[CH3:21][O:10][C:9](=[O:11])[CH:8]([NH:12][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1Participants
Conditions
- Temperature
- 40 °C
Procedure
4Fluoro-α-[(phenylmethyl)amino]benzeneacetic acid (12.2 kg, 47.1 moles) was slurried in methanol (37 L), then hydrogen chloride gas was passed over the mixture. The resulting slurry was stirred at 35-45° C. for 3 hours, then concentrated to 30-35 L by distillation. Methyl-t-butyl ether (20 L) was added and the batch was seeded with 4-Fluoro-α-[(phenylmethyl)amino]benzeneacetic acid methyl ester hydrochloride. Upon development of the seed-bed, methyl-t-butyl ether (20 L) was added. The slurry was aged for 1 hour, then filtered. The filter cake was washed with methyl-t-butyl ether:methanol (95:5, 8.0 L), then dried under vacuum at 30° C. to give 12.2 kg (84% yield) of 4-fluoro-α-[(phenylmethyl)amino]benzeneacetic acid methyl ester hydrochloride.
Workup
- concentrationconcentrated to 30-35 L by distillation
- additionMethyl-t-butyl ether (20 L) was added
- additionUpon development of the seed-bed, methyl-t-butyl ether (20 L) was added
- waitThe slurry was aged for 1 hour
- filtrationfiltered
- washThe filter cake was washed with methyl-t-butyl ether:methanol (95:5, 8.0 L)
- customdried under vacuum at 30° C.
Sources & evidence
- ORD record
- ord-1b6125cbcbc84526a2e3d5be60428d6e
- Source dataset
- uspto-grants-2001_05
- Patent number
- US06235735B1
Reaction notes
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