Process for the synthesis of long-chain fatty acids

1. A compound of Formula II:

or salt thereof; wherein:

L 1 is selected from C 4-50 straight-chain alkylene and C 4-50 straight-chain alkenylene; each of which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R a groups;

L 2 is selected from C 4-50 straight-chain alkylene and C 4-50 straight-chain alkenylene; each of which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R b groups;

R 1 is phenyl, which is optionally substituted by 1, 2, 3, 4, or 5 independently selected R 1a groups;

each R 1a is independently selected from halogen, cyano, nitro, hydroxyl, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, di(C 1-6 alkyl)amino, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 )alkylcarbamyl, C 1-6 alkoxycarbonyl, and C 1-6 alkylsulfonyl; and

each R a and R b is independently selected from C 1-30 alkyl and C 2-30 alkenyl.

2. A compound according to claim 1 or salt thereof, wherein R 1 is phenyl.

3. A compound of Formula II:

or salt thereof; wherein:

L 1 is C 8-50 straight-chain alkylene; which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R a groups;

L 2 is selected from C 4-50 straight-chain alkylene and C 4-50 straight-chain alkenylene; each of which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R b groups;

R 1 is phenyl, which is optionally substituted by 1, 2, 3, 4, or 5 independently selected R 1a groups;

each R 1a is independently selected from halogen, cyano, nitro, hydroxyl, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, di(C 1-6 alkyl)amino, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 )alkylcarbamyl, C 1-6 alkoxycarbonyl, and C 1-6 alkylsulfonyl; and

each R a and R b is independently selected from C 1-30 alkyl and C 2-30 alkenyl.

4. A compound of Formula II:

or salt thereof; wherein:

L 1 is C 8-50 straight-chain alkylene;

L 2 is selected from C 4-50 straight-chain alkylene and C 4-50 straight-chain alkenylene; each of which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R b groups;

R 1 is phenyl, which is optionally substituted by 1, 2, 3, 4, or 5 independently selected R 1a groups;

each R 1a is independently selected from halogen, cyano, nitro, hydroxyl, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, di(C 1-6 alkyl)amino, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 )alkylcarbamyl, C 1-6 alkoxycarbonyl, and C 1-6 alkylsulfonyl; and

each R b is independently selected from C 1-30 alkyl and C 2-30 alkenyl.

5. A compound of Formula II:

or salt thereof; wherein:

L 1 is selected from C 4-50 straight-chain alkylene and C 4-50 straight-chain alkenylene; each of which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R a groups;

L 2 is selected from C 10-50 straight-chain alkylene and C 10-50 straight-chain alkenylene; which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R b groups;

R 1 is phenyl, which is optionally substituted by 1, 2, 3, 4, or 5 independently selected R 1a groups;

each R 1a is independently selected from halogen, cyano, nitro, hydroxyl, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, di(C 1-6 alkylamino, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 )alkylcarbamyl, C 1-6 alkoxycarbonyl, and C 1-6 alkylsulfonyl; and

each R a and R b is independently selected from C 1-30 alkyl and C 2-30 alkenyl.

6. A compound of Formula II:

or salt thereof; wherein:

L 1 is selected from C 4-50 straight-chain alkylene and C 4-50 straight-chain alkenylene; each of which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R a groups;

L 2 is selected from C 10-50 straight-chain alkylene and C 10-50 straight-chain alkenylene;

R 1 is phenyl, which is optionally substituted by 1, 2, 3, 4, or 5 independently selected R 1a groups;

each R 1a is independently selected from halogen, cyano, nitro, hydroxyl, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, di(C 1-6 alkyl)amino, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 )alkylcarbamyl, C 1-6 alkoxycarbonyl, and C 1-6 alkylsulfonyl; and

each R a is independently selected from C 1-30 alkyl and C 2-30 alkenyl.

7. A compound according to claim 6 , or salt thereof, wherein L 2 is C 10-50 straight-chain alkenylene.

8. A compound of Formula II:

or salt thereof; wherein:

L 1 is selected from C 4-50 straight-chain alkylene and C 4-50 straight-chain alkenylene; each of which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R a groups;

L 2 is selected from C 4-50 straight-chain alkylene and C 4-50 straight-chain alkenylene; each of which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R b groups;

R 1 is phenyl, which is optionally substituted by 1, 2, 3, 4, or 5 independently selected R 1a groups;

each R 1a is independently selected from halogen, cyano, nitro, hydroxyl, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, di(C 1-6 alkyl)amino, carbamyl, C 1-6 alkylcarbamyl, di(C 1-6 )alkylcarbamyl, C 1-6 alkoxycarbonyl, and C 1-6 alkylsulfonyl; and

each R a and R b is independently selected from C 1-30 alkyl and C 2-30 alkenyl; wherein the moiety L 2 -CH 2 -L 1 is at least 20 carbons in length.

9. A compound according to claim 1 , or salt thereof, wherein the moiety L 2 -CH 2 -L 1 is at least 25 carbons in length.

10. A process of preparing a compound of Formula I:

or salt thereof; comprising desulfonating a compound of formula II according to claim 1 , or salt thereof, to form a compound of Formula I.

11. The process according to claim 10 , wherein the desulfonating comprises treating with sodium-mercury amalgam.

12. The process according to claim 10 , further comprising preparing the compound of Formula II:

or salt thereof, by a process comprising oxidizing a compound of Formula III:

or salt thereof.

13. The process according to claim 12 , wherein the oxidizing comprises treating with chromium trioxide and sulfuric acid.

14. The process according to claim 12 , further comprising preparing the compound of Formula III, or salt thereof, by a process comprising deprotecting a compound of Formula IV:

to form the compound of Formula III:

wherein P 1 is a hydroxyl protecting group.

15. The process according to claim 14 , wherein P 1 is tert-butyldimethylsilyl.

16. The process according to claim 14 , wherein the deprotecting comprises treating with tetrabutylammonium fluoride.

17. The process according to claim 14 , further comprising preparing the compound of Formula IV:

by a process comprising treating a compound of Formula V:

with a strong base, followed by reacting with a compound of Formula VI:

to form the compound of Formula IV;

wherein Y is a leaving group.

18. The process according to claim 14 , further comprising preparing the compound of Formula IV:

by a process comprising reacting a compound of Formula XII:

with a compound of Formula XIII:

to form the compound of Formula IV.

19. The process according to claim 17 , wherein Y is p-toluenesulfonyloxy.

20. The process according to claim 17 , wherein the strong base is n-butyllithium.

21. The process according to claim 17 , further comprising preparing the compound of Formula V:

by a process comprising oxidizing a compound of Formula VII:

to form the compound of Formula V.

22. The process according to claim 21 , wherein the oxidizing comprises treating with m-chloroperoxybenzoic acid.

23. The process according to claim 21 , further comprising preparing the compound of Formula VII:

by a process comprising reacting a compound of Formula VIII:

with a compound of formula R 1 SH in the presence of a strong base to form the compound of Formula VII;

wherein X is a leaving group.

24. The process according to claim 23 , wherein the strong base is sodium methoxide.

25. The process according to claim 23 , wherein X is halogen.

26. The process according to claim 23 , wherein X is bromo.

27. The process according to claim 23 , further comprising preparing the compound of Formula VIII:

by a process comprising protecting a compound of Formula IX:

to form a compound of Formula VIII.

28. The process according to claim 17 , further comprising preparing the compound of Formula VI:

by a process comprising:

(a) reducing a compound of Formula X:

or salt thereof, to form a compound of Formula XI:

and

(b) converting the compound of Formula XI to the compound of Formula VI; wherein:

Y is a leaving group;

L 2 is selected from C 4-50 straight-chain alkylene and C 4-50 straight-chain alkenylene; each of which is optionally substituted with 1, 2, 3, 4, 5, or 6 independently selected R b groups; and

each R b is independently selected from C 1-30 alkyl and C 2-30 alkenyl.

29. A process according to claim 28 , wherein the reducing comprises treating with lithium aluminum hydride.

30. A process according to claim 28 , wherein Y is p-toluenesulfonyloxy.

31. A process according to claim 28 , wherein the converting comprises reacting with p-toluenesulfonyl chloride.