P-Toluenesulfonylhydrazide → Methylphenidate Hydrochloride Impurity 16

HRID 1296786Notes

Reaction equation

[C:1]1([C:7](=O)[C:8]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:17]1([CH3:28])[CH:22]=[CH:21][C:20]([S:23]([NH:26][NH2:27])(=[O:25])=[O:24])=[CH:19][CH:18]=1>S(=O)(=O)(O)O.C(O)C>[C:17]1([CH3:28])[CH:18]=[CH:19][C:20]([S:23]([NH:26][N:27]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:8]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)=[O:9])(=[O:24])=[O:25])=[CH:21][CH:22]=1

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of 98% sulfuric acid (121.7 g, 1.22 mol, 0.02 eq) in abs ethanol (1.0 L) was added dropwise to a stirred mixture of 1-(phenylglyoxylyl)piperidine (17.58 Kg, 80.9 mol, 1 eq), p-toluenesulfonhydrazide (16.20 Kg, 87.0 mol, 1.08 eq) and abs ethanol (50 L) at 20-30° C. The obtained mixture was stirred under reflux conditions until 1-(phenylglyoxylyl)piperidine disappeared (˜7 hours, TLC control). The mixture was stirred for 1 hour at 20-30° C. and kept overnight at 4-6° C. The precipitated solid was filtered off, washed on the filter with cold methanol and cold hexane and dried under reduced pressure to a constant weight to yield 28.25 Kg (90.6%) of 1-(phenylglyoxylyl)piperidine p-toluenesulfonylhydrazone with 99.9% purity by HPLC.

Workup

custom(˜7 hours, TLC control)
waitkept overnight at 4-6° C
filtrationThe precipitated solid was filtered off
washwashed on the
filtrationfilter with cold methanol and cold hexane
customdried under reduced pressure to a constant weight

Sources & evidence

ORD record: ord-9a3b549bb94d452b9031c4fd14c2e7e7
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07247730B2

Reaction notes

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