Process for production of pentahydroxyhexylcarbamoyl alkanoic acids

1. A process for preparing a compound of formula:

wherein n is an integer from 6 to 17

comprising the steps of:

a) reacting a monoester of a dioic acid of formula

wherein R is chosen from benzyl, substituted benzyl, allyl, 2-(trimethylsilyl)ethyl, and 9-fluorenylmethyl, with 2,3,4,5,6-pentahydroxyhexylamine to form an ester/amide of formula

and

b) reacting said ester/amide with a reagent to cleave said ester and provide said compound of formula I.

2. A process according to claim 1 wherein R is chosen from allyl, 2-(trimethylsilyl)ethyl and 9-fluorenylmethyl and said reagent for cleaving said ester is chosen from a palladium catalyst, fluoride anion and piperidine or diethylamine, respectively.

3. A process according to claim 1 comprising the steps of

a) coupling a monoester of dodecanedioic acid of formula:

with D-glucamine to form an amide of formula Ia:

and

hydrogenolyzing the compound of formula IIA to a compound of formula Ia:

4. The process of claim 3 wherein the hydrogenolysis is carried out in the presence of a noble metal catalyst and a source of hydrogen.

5. A process according to any of claims 1 – 4 wherein said monoester is obtained by reacting dodecanedioic acid with a formate ester of the corresponding alcohol ROH in the presence of an acid catalyst.

6. A process according to claim 5 wherein said acid catalyst is a sulfonic acid ion exchange resin.

7. A process according to claim 6 wherein said monoester is obtained by reacting dodecanedioic acid with benzyl formate.

8. A process according to claim 7 comprising the steps of

a) reacting dodecanedioic acid with benzyl formate in the presence of a sulfonic acid ion exchange resin to provide a monoester of dodecanedioic acid of formula:

b) coupling said monoester of dodecanedioic acid

with D-glucamine to form an amide of formula Ia:

and

c) hydrogenolyzing the compound of formula IIA with palladium and hydrogen to provide a compound of formula Ia:

9. A process according to claim 3 for preparing dodecanedioic acid 4-[(2S,3R)-3-[(S)-3-(4-fluorophenyl)-3-hydroxypropyl]-2-(4-methoxyphenyl)-4-oxoazetidin-1-yl]benzylamide ((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxyhexyl)amide comprising the additional step of condensing said compound of formula Ia with 4-[(2S,3R)-3-[(S)-3-(4-fluorophenyl)-3-hydroxypropyl]-2-(4-methoxyphenyl)-4-oxoazetidin-1-yl]benzylamine.

10. A compound of formula:

wherein n is an integer from 6 to 17.

11. A compound according to claim 10 of formula: