Methanesulfonic Acid → Safinamide Mesylate

HRID 2061154Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[CH2:5][O:6][C:7]1[CH:19]=[CH:18][C:10]([CH2:11][NH:12][C@@H:13]([CH3:17])[C:14]([NH2:16])=[O:15])=[CH:9][CH:8]=1.[CH3:23][S:24]([OH:27])(=[O:26])=[O:25]>C(OCC)(=O)C>[CH3:23][S:24]([OH:27])(=[O:26])=[O:25].[F:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:11][NH:12][C@@H:13]([CH3:17])[C:14]([NH2:16])=[O:15])=[CH:18][CH:19]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of (S)-2[4-(3-fluorobenzyloxy)benzylamino]propanamide (1.50 g, 4.96 mmol) and ethyl acetate (40.2 mL) is heated to 50° C. until a clear solution is obtained. Methanesulfonic acid (0.53 g, 5.51 mmol) is added under stirring in 15 minutes to the solution and the resulting heterogeneous mixture is cooled under stirring to 20° C. in 90 minutes. After 30 minutes at 20° C. the solid is collected by filtration, washed with ethyl acetate (6 mL) and dried at 50° C. at reduced pressure for 15 hrs to provide (S)-2[4-(3-fluorobenzyloxy)benzylamino]propanamide methanesulfonate (Ic) as a white solid in a 96.1% yield. The product has HPLC purity 98.6 (area %, see Example 17A) and a content of (S)-2-[3-(3-fluorobenzyl)-4-(3-fluorobenzyloxy)-benzylamino]propanamide methanesulfonate (IIc) of 0.10% by weight determined by HPLC (see Example 17B).

Workup

customis obtained
temperaturethe resulting heterogeneous mixture is cooled
stirringunder stirring to 20° C. in 90 minutes
filtrationAfter 30 minutes at 20° C. the solid is collected by filtration
washwashed with ethyl acetate (6 mL)
customdried at 50° C. at reduced pressure for 15 hrs

Sources & evidence

ORD record: ord-54d14dd4e7c54686ace587cfbf1115c8
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08278485B2

Reaction notes

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