Zopiclone → 6-(5-Chloro-2-pyridyl)-6,7-dihydro-7-hydroxy-5H-pyrrolo(3,4-b)pyrazin-5-one

HRID 507806

Reaction equation

HRID 507806 reaction equation
CN1CCN(C([O:10][CH:11]2[N:20]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][N:22]=3)[C:18](=[O:19])[C:17]3[C:12]2=[N:13][CH:14]=[CH:15][N:16]=3)=O)CC1>Cl>[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([N:20]2[CH:11]([OH:10])[C:12]3[C:17](=[N:16][CH:15]=[CH:14][N:13]=3)[C:18]2=[O:19])=[N:22][CH:23]=1

Participants

3

Reactant 1

HCID 5735Zopiclone

Product 1

HCID 64519726-(5-Chloro-2-pyridyl)-6,7-dihydro-7-hydroxy-5H-pyrrolo(3,4-b)pyrazin-5-one

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
70 °C

Procedure

(R)-Zopiclone (50 g) was dissolved in 10% HCl (500 ml) and heated up to 70° C. for 3 hrs. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mass was cooled to room temperature, further cooled to 0° C. to 5° C. and filtered to obtain 6-(5-chloropyrid-2-yl)-5-hydroxy-7-oxo-5,6-dihydro-pyrrolo-[3,4-b]pyrazine. (22.4 g). Charged 22.4 g of 6-(5-chloropyridyl-2-yl)-5-hydroxy-7-oxo-5,6-dihydro-5H-pyrrolo[3,4-b]pyrazine in 250 ml of methylene chloride and the reaction mixture cooled to 5-10° C. 22.4 g of 1-chlorocarbonyl-4-methylpiperazine hydrochloride was added at the same temperature. 27.32 g of triethyl amine was added to the reaction mixture followed by addition of N,N-dimethylamino pyridine (0.8 gms) at temperature 5-10° C. in two lots. Reaction mixture was heated to reflux and maintained for 2 hrs. Reaction mixture was cooled to room temperature and 100 ml. of water was added at 25° C. The organic layer was separated and aqueous phase was extracted with methylene chloride (50 ml). The combined organic phase was washed with water (50 ml), the organic phase was separated and concentrated at atmospheric pressure to obtain crude zopiclone. The crude zopiclone was recrystallised from ethyl acetate and further purified from isopropanol (Yield: 26.8 gms). The racemic zopiclone thus obtained was resolved using the method given in example 4 to obtain eszopiclone.

Workup

  1. customAfter completion of the reaction
  2. temperaturethe reaction mass was cooled to room temperature
  3. temperaturefurther cooled to 0° C. to 5° C.
  4. filtrationfiltered

Sources & evidence

ORD record
ord-06da48bbcca5453eafba9682995d017e
Source dataset
uspto-grants-2010_08
Patent number
US07786304B2

Linked notes

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