US 12,391,635 B2
Oxidation of santalene to santalol
Dominique Callant, Geleen (NL); Paul Alsters, Geleen (NL); Karin Dautzenberg, Geleen (NL); Angela Gonzalez De Castro, Geleen (NL); and Robert Trokowski, Geleen (NL)
Assigned to ISOBIONICS B.V., Geleen (NL)
Appl. No. 17/764,559
Filed by ISOBIONICS B.V., Geleen (NL)
PCT Filed Sep. 25, 2020, PCT No. PCT/EP2020/076917
§ 371(c)(1), (2) Date Mar. 29, 2022,
PCT Pub. No. WO2021/063831, PCT Pub. Date Apr. 8, 2021.
Claims priority of application No. 2023931 (NL), filed on Oct. 2, 2019.
Prior Publication US 2022/0371976 A1, Nov. 24, 2022
Int. Cl. C07C 29/09 (2006.01); C07C 17/10 (2006.01); C07C 22/02 (2006.01); C07C 67/11 (2006.01)
CPC C07C 29/095 (2013.01) [C07C 17/10 (2013.01); C07C 22/02 (2013.01); C07C 67/11 (2013.01); C07C 2601/16 (2017.05); C07C 2602/42 (2017.05); C07C 2603/64 (2017.05); C07C 2603/66 (2017.05)] 12 Claims
 
1. A process for the synthesis of a mixture of compounds of Formula (Ia), Formula (Ib), Formula (Ic), Formula (Id) and Formula (Ie),

OG Complex Work Unit Chemistry
wherein R=a, b, c, d or e;

OG Complex Work Unit Chemistry
and wherein Formula (Ia) corresponds to Formula (I) where R is a, Formula (Ib) corresponds to Formula (I) where R is b, Formula (Ic) corresponds to Formula (I) where R is c, Formula (Id) corresponds to Formula (I) where R is d, and Formula (Ie) corresponds to Formula (I) where R is e,
the method comprising
(1) chlorinating a mixture of compounds of Formula (II) by combining the starting compounds of Formula (II) with an acid and an aqueous NaOCl solution, wherein the mixture of compounds of Formula (II) comprises the compounds of Formula (IIa), Formula (IIb), Formula (IIc), Formula (IId) and Formula (IIe)

OG Complex Work Unit Chemistry
wherein Formula (IIa) corresponds to Formula (II) where R is a, Formula (IIb) corresponds to Formula (II) where R is b, Formula (IIc) corresponds to Formula (II) where R is c, Formula (IId) corresponds to Formula (II) where R is d, and Formula (IIe) corresponds to Formula (II) where R is e,
to a mixture of intermediates of Formula (IIIa), Formula (IIIb), Formula (IIIc) and Formula (IIIe) and a di-chlorinated and/or a tri-chlorinated analogue of intermediate of Formula (IIId)

OG Complex Work Unit Chemistry
wherein Formula (IIIa) corresponds to Formula (III) where R is a, Formula (IIIb) corresponds to Formula (III) where R is b, Formula (IIIc) corresponds to Formula (III) where R is c, Formula (IIId) corresponds to Formula (III) where R is d, and Formula (Ille) corresponds to Formula (III) where R is e,
wherein the chlorinating step comprises
converting the starting compounds of Formula (IIa), Formula (IIb), Formula (IIc) and Formula (IIe) to the intermediates of Formula (IIIa), Formula (IIIb), Formula (IIIc) and Formula (IIIe); and
introducing two or three chloro-substituents on the starting compound of Formula (IId) to yield the di-chlorinated and/or tri-chlorinated analogue of the intermediate of Formula (IIId);
conversion of (2) converting a mixture of intermediates of Formula (IIIa), Formula (IIIb), Formula (IIIc) and Formula (IIIe) to a mixture of compounds of Formula (Ia), Formula (Ib), Formula (Ic) and Formula (Ie) by
reacting the intermediate of Formula (III) with a carboxylate R′—COO− to form the corresponding carboxylate ester of Formula (IV), wherein the carboxylate is selected from the group consisting of acetate, formate, propionate, butyrate, valerate, benzoate, pivalate, and mixtures thereof

OG Complex Work Unit Chemistry
and hydrolyzing the carboxylate ester of Formula (IV) to obtain the mixture of compounds of Formula (Ia), Formula (Ib), Formula (Ic) and Formula (Ie),
wherein the di-chlorinated and/or tri-chlorinated analogue of the intermediate of Formula (IIId) is removed from the mixture prior to or during the conversion of intermediates of Formula (IIIa), Formula (IIIb), Formula (IIIc), and Formula (IIIe) to the mixture of compounds of Formula (Ia), Formula (Ib), Formula (Ie) and Formula (Ie).