L-Malic Acid → (S)-Zopiclone L-Malate

HRID 44215

Reaction equation

[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C@@H:11]2[N:20]([C:21]3[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][N:26]=3)[C:18](=[O:19])[C:13]3[N:14]=[CH:15][CH:16]=[N:17][C:12]2=3)=[O:9])[CH2:4][CH2:3]1.[C:28]([OH:36])(=[O:35])[C@H:29]([CH2:31][C:32]([OH:34])=[O:33])[OH:30]>C(O)C>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C@@H:11]2[N:20]([C:21]3[CH:22]=[CH:23][C:24]([Cl:27])=[CH:25][N:26]=3)[C:18](=[O:19])[C:13]3[N:14]=[CH:15][CH:16]=[N:17][C:12]2=3)=[O:9])[CH2:4][CH2:3]1.[C:28]([O-:36])(=[O:35])[C@H:29]([CH2:31][C:32]([O-:34])=[O:33])[OH:30]

Participants

Conditions

Temperature: 65 °C

Procedure

A reactor was charged with 5.67 g (S)-zopiclone and 194 g ethanol (SDA 3A). The mixture was heated to 65° C., and to the reactor was added a solution created by combining 2.05 g of L-malic acid with 18.5 g ethanol. The reaction was rinsed in with 26 g ethanol. The mixture was seeded with 100 mg powdered (S)-zopiclone-L-malate, and aged for 60 minutes. The mixture was cooled to 40° C. at 0.3° C./minute and aged for 30 mins. The mixture was cooled to 20° C. at 0.5° C./minute and aged for 30 mins. The mixture was filtered, washed with 20 g ethanol in one wash, dried in vacuo until no further weight loss at approximately 50° C. (˜6 h), to provide the titled compound in 86% yield.

Workup

additionto the reactor was added a solution
washThe reaction was rinsed in with 26 g ethanol
temperatureThe mixture was cooled to 40° C. at 0.3° C./minute and aged for 30 mins
temperatureThe mixture was cooled to 20° C. at 0.5° C./minute and aged for 30 mins
filtrationThe mixture was filtered
washwashed with 20 g ethanol in one
washwash
customdried in vacuo until no further weight loss at approximately 50° C. (˜6 h)

Sources & evidence

ORD record: ord-956cdfa0e53d4f59b97b2addb559eda0
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541416B2

Linked notes

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