Organocatalytic process for asymmetric synthesis of decanolides

Patent metadata

Field	Value
Publication number	US-9765048-B2
Application number	US-201615167298-A
Country	US
Kind code	B2
Filing date	May 27, 2016
Priority date	Sep 6, 2012
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

Abstract

The present invention discloses organocatalytic process for asymmetric synthesis of highly enantioselective decanolide compounds in high yield with >99% ee. Further, the present invention disclose cost effective, improved organocatalytic process for asymmetric synthesis of highly enantioselective decanolides compounds from non-chiral, cheap, easily available raw materials.

First claim

We claim:

1. An organo catalytic process for preparation of a compound of Formula Ib

wherein, the said process comprising the steps of:
i) protecting one of the terminal hydroxyl group of diol (21)

with benzyl group by using benzyl bromide in dry THF to obtain corresponding mono-benzyl ether (22),

followed by oxidization in presence of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl and iodobenzene diacetate in organic solvent selected from DCM, DMF to obtain benzyl protected aldehyde (23)

ii) proline-catalyzed direct asymmetric α-aminoxylation of benzyl protected aldehyde (23) using nitrosobenzene in acetonitrile as an oxygen source, followed by treatment with NaBH 4 in methanol further treating with copper (II) acetate in methanol for 24 hours (10-20 mins) at temperature ranging between to obtain chiral diol (24),

which is further treated with dibutyl tin oxide and tosyl chloride, triethylamine in DCM furnishes the mono tosylated compound, which is further treated with potassium carbonate in dry methanol at 0-25° C. for 20-40 mins to obtain epoxy compound (25)

iii) reducing epoxy compound (25) in presence of LAH to chiral secondary alcohol (26),

subsequently protecting with TBS by using TBS-Cl, imidazole in DCM followed by deprotection of benzyl in presence of palladium catalyzed reduction in ethyl acetate gives TBS protected alcohol (28);

followed by oxidization in presence of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl and iodobenzene diacetate in organic solvent preferably DCM to obtain aldehyde compound (29)

iv) contacting compound (29) with L-proline, PhNO, MeCN, then triethyl phosphonoacetate, DBU, LiCl then Cu(OAc) 2 to yield hydroxyl ester (30),

further protecting with MOM in presence of MOMCl and DIPEA in DCM to corresponding protected ester (31)

v) reducing the protected ester (31) using DIBAL-H in dry DCM at temperature range from −70° C. to −85° C. to obtain aldehyde (32),

followed by Wittig reaction in dry THF at temperature range from −70° C. to −85° C. to obtain corresponding ester (33);

further deprotecting of TBS in presence of TBAF in THF to secondary alcohol (34),

followed by alkali hydrolysis of the ester with LiOH in methanol and water to carboxylic acid (35)

vi) contacting (35) with 2,4,6 trichloro benzoyl chloride and triethylamine in THF and DMAP in toluene to obtain the MOM protected decanolide (36)

subsequently deprotecting of MOM to obtain decanolides of Formula Ib.

Assignees

• Council Scient Ind Res

Inventors

• Rawat Varun
• Dey Soumen
• Shelke Anil Maruti
• Suryavanshi Gurunath Mallappa
• Sudalai Arumugam

Classifications

• C07D313/00 Primary

  Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom · CPC title

• C07B2200/07

  Optical isomers · CPC title