Methanesulfonic Acid → Safinamide Mesylate

HRID 41741Notes

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 min to the solution and the resulting heterogeneous mixture is cooled under stirring to 20° C. in 90 min. After 30 min 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 25A) 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 25B).

Workup

customis obtained
temperaturethe resulting heterogeneous mixture is cooled
stirringunder stirring to 20° C. in 90 min
filtrationAfter 30 min 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-70bfeb2ab17e48e097b7f8b509f10214
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530701B2

Reaction notes

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