Claims
- 1. A solvent-free method for synthesizing 1,2:5,6-di-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose comprising the steps of:
- forming, in the absence of solvent, a single mixture containing 1,2:5,6-di-O-isopropylidene-.alpha.,D-glucofuranose, a halodimethylaminopropane, and an anhydrous alkali base;
- heating said mixture to a temperature sufficient to allow said mixture to react;
- maintaining said mixture at a temperature of at least about 110.degree. C. for a time sufficient to form 1,2:5,6-di-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose and drive off any water produced;
- removing any unreacted halodimethylaminopropane from said mixture; and
- recovering said 1,2:5,6-di-O-isopropylidene-3-O-3'-(N',N'-dimethylanmino-n-propyl)-.alpha.,D-glucofuranose.
- 2. The method of claim 1, wherein said mixture contains 0.1-0.2 molar excess of said halodimethylaminopropane and 2 molar excess of said anhydrous alkali base.
- 3. The method of claim 2, wherein said halodimethylaminopropane is chlorodimethylaminopropane and said anhydrous alkali base is sodium hydroxide.
- 4. The method of claim 1, wherein said halodimethylaminopropane is chlorodimethylaminopropane and said anhydrous alkali base is sodium hydroxide.
- 5. The method of claim 2, wherein said removal step is accomplished under reduced pressure.
- 6. The method of claim 2, wherein said recovery step comprises the steps of
- dissolving said 1,2:5,6-di-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose in an organic solvent which is immiscible with water;
- separating any solids from the resultant solution;
- washing said solution with water to yield a liquid system containing a separate aqueous phase and a separate organic phase;
- separating the aqueous phase from the organic phase; and
- recovering said 1,2:5,6-di-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose from the organic phase.
- 7. The method of claim 6, further comprising, after said recovery step, the step of selectively hydrolyzing said 1,2:5,6-di-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose to form 1,2-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose or the acid addition salt thereof.
- 8. The method of claim 3 wherein said selective hydrolysis is carried out using about 2 molar equivalents of H.sub.2 O in 20% HCl in an ethanol environment.
- 9. The method of claim 8, further comprising the steps of washing said 1,2-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose or the acid addition salt thereof with alcohol; and
- drying said 1,2-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose or the acid addition salt thereof.
- 10. The method of claim 2, further comprising, after said recovery step, the step of selectively hydrolyzing said 1,2:5,6-di-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose to form 1,2-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose or the acid addition salt thereof.
- 11. The method of claim 1, further comprising, after said recovery step, the step of selectively hydrolyzing said 1,2:5,6-di-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose to form 1,2-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose or the acid addition salt thereof.
- 12. The method of claim 11, wherein said halodimethylaminopropane is chlorodimethylaminopropane, and said anhydrous alkali base is sodium hydroxide.
- 13. The method of claim 1, wherein said mixture is maintained at a temperature of from about 110.degree. C. to about 135.degree. C.
- 14. The process of claim 1, wherein said mixture is maintained at a temperature of from about 110.degree. C. to about 120.degree. C.
- 15. The process of claim 1, wherein said mixture is heated to a temperature of at least about 80.degree. C.
- 16. The process of claim 1, wherein said time sufficient to form 1,2:5,6-di-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose and drive off any water produces is from about 30 minutes to about 120 minutes.
- 17. A solvent-free synthesis to prepare 1,2:5,6-di-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose by the following reaction: ##STR4## wherein R is a dimethylaminopropyl group, X is chloro, and the reactants are combined in a single mixture which is heated at a temperature of at least about 110.degree. C. for a time sufficient to form 1,2:5,6-di-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose.
- 18. The method of claim 17, further comprising the step of selectively hydrolyzing said 1,2:5,6-di-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose to form 1,2-O-isopropylidene-3-O-3'-(N',N'-dimethylamino-n-propyl)-.alpha.,D-glucofuranose or the acid addition salt thereof.
Parent Case Info
This application is a continuation of application Ser. No. 07/658,311, filed Feb. 20, 1991, now abandoned.
US Referenced Citations (16)
Non-Patent Literature Citations (1)
Entry |
Wayne G. Riskin, et al., "Amiprilose Hydrochloride for Rheumatoid Arthritis", Annals of Internal Medicine, vol. 111, No. 6, Sep. 15, 1989, pp. 455-465. |
Continuations (1)
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Number |
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658311 |
Feb 1991 |
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