Synthesis of isohexide dicarbamates and derivatives thereof

Patent metadata

Field	Value
Publication number	US-9422304-B2
Application number	US-201414781362-A
Country	US
Kind code	B2
Filing date	May 7, 2014
Priority date	Jun 12, 2013
Publication date	Aug 23, 2016
Grant date	Aug 23, 2016

Abstract

Isohexide dicarbamates and a method of preparing the same are described. The method involves reacting a mixture of an isohexide and a cynate salt in a non-aqueous solvent, with a miscible acid having a pKa of about 3.7 or less. The isohexide dicarbamates can serve as precursor materials from which various derivative compounds can be synthesized.

First claim

I claim:

1. A process for preparing dicarbamates of 1,4:3,6-dianhydrohexitols, the process comprising: providing a mixture of an isohexide with a cyanate salt in an inert organic solvent, reacting said mixture with an acid having a pK a ≦3.7.

2. The process according to claim 1 , wherein said acid is added to said reaction mixture of isohexide at a rate of about 0.03-0.1 stoichiometric equivalents per minute.

3. The process according to claim 1 , wherein said isohexide is at least: a) isosorbide, b) isomannide, and c) isoidide.

4. The process according to claim 1 , wherein said organic solvent at least: methylene chloride, chloroform, carbon tetrachloride, benzene, toluene, xylenes, linear and/or branched alkanes, tetrahydrofuran, 1,4-dioxane, dimethylsulfoxide, acetonitrile, dimethylformamide, acetic acid, HMPT, nitromethane, pyridine, N-methyl pyrolidinone, dimethylacetamide, ethyl acetate, acetone, methyl tert-butyl ether, diethyl ether.

5. The process according to claim 1 , wherein said cyanate salt having a cationic counter-ion selected from the group consisting of: Na, K, Li, Ag, Hg, Al, Ca, Mg, Pb, Sn, Ti, Ni, Cs, Rb, Cu, Zn, Cd, In, Co, Ga, Ba, Pd, Pt, Tl, Fr, Sb, Ge, Sr, Be, V, Bi, Mo, Mn, Fe, Nb, Cr, Eu, organic cations of ammonium, pyridinium, and a combination of the foregoing.

6. The process according to claim 1 , wherein said acid is either an organic acid or a mineral acid.

7. The process according to claim 6 , wherein when said acid is an organic acid, said acid is at least: trifluoro-acetic acid (TFA) trichloro-acetic acid, oxalic acid, pyruvic acid, malonic acid, furamic acid, maleic acid, malic acid, tartaric acid, picric acid, electron deficient benzoic acids (mono, di, and tri-nitro, cyano, trifluoro), terephthalic acid, methanesulfonic acid, p-toluenesulfonic acid, and trifluoromethylsulfonic acid.

8. The process according to claim 6 , wherein when said acid is a mineral acid, said acid is at least: sulfuric acid, hydrogen halides (HCl, HBr, HI), perchloric acid, phosphoric acid, and boric acid.

9. The process according to claim 1 , wherein said reaction is conducted at a temperature in a range from about 0° C. to about 55° C.

10. The process according to claim 1 , further comprising purifying said isohexide dicarbamates according to a protocol involving a simple filtration, washing, and drying under high vacuum.

11. The process according to claim 1 , wherein said process results in at least a 55% yield of corresponding isohexide dicarbamates.

12. The process according to claim 11 , wherein said process results in about a 70% or greater yield of corresponding isohexide dicarbamates.

Assignees

• Archer Daniels Midland Co

Inventors

• Stensrud Kenneth

Classifications

• A61K31/343

  condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone · CPC title

• A61K31/428

  condensed with carbocyclic rings · CPC title

• C07D307/42 Primary

  Singly bound oxygen atoms · CPC title

• C07D493/04 Primary

  Ortho-condensed systems · CPC title

• A61K31/40

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title