Process for Preparing Hydrocodone Using a Super Acid
AssigneeMallinckrodt Inc.
InventorsPeter X. Wang, Tao Jiang, Subo Liao, Erin Moore
Life of this patent
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Abstract
The present disclosure generally relates to a process for converting a fused, tricyclic compound to a fused, tetracyclic compound that includes a furan ring therein. More particularly, the present disclosure related to a process for preparing a hydrocodone compound, or a compound structurally related thereto, and in particular (+)-hydrocodone, by subjecting a structurally corresponding sinomenine starting compound to a super acid-assisted furan ring closure reaction.
Claims25
A process for carrying out a furan ring closure reaction to transform a compound having a structure of Formula (I) to a compound having a structure of Formula (II):
- wherein:
- R is selected from the group consisting of hydrogen, acyl, trialkylsilyl, tertiary-alkyl, aryl-substituted methyl, and alkoxy carbonyl;
- X represents 3 substituents on the A ring, which may be the same or different and which are independently selected from hydrogen, halogen, alkoxy, cyano, hydrocarbyl, substituted hydrocarbyl and NRcRd, where each of Rc and Rd are independently selected from the group consisting of hydrogen, hydroxy and hydrocarbyl;
- Y represents 5 or 6 substituents on the B ring, which may be the same or different and which are independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heterohydrocarbyl, and substituted heterohydrocarbyl, with the proviso that when Y represents 5 substituents, at least one of the substituents forms a bridge between two carbon atoms in the B ring;
- and
- Z represents between 3 and 5 substituents on the C ring, which may be the same or different and which may be independently selected from H, hydroxy, hydrocarbyl, substituted hydrocarbyl, heterohydrocarbyl, and substituted heterohydrocarbyl, with the provisos that (i) at least one of the Z substituents is hydroxy or alkoxy at either the C5 or C7 position on the C ring, and (ii) when Z represents 3 substituents, the C ring includes a carbon-carbon double bond therein;
- the process comprising contacting the compound of Formula (I) with a super acid under process conditions suitable for forming a bond between the oxygen of the —OR substituent of the A ring and a carbon atom of the C ring, such that a furan ring is formed.
A process for carrying out a furan ring closure reaction to transform a compound of Formula (III) to a compound of Formula (IV):
- wherein:
- R1 and R2 are independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, cyano, hydrocarbyl, substituted hydrocarbyl and NRcRd, where each of Rc and Rd are independently selected from the group consisting of hydrogen, hydroxy and hydrocarbyl;
- R3 and R5 are independently selected from the group consisting of hydrogen, hydrocarbyl and substituted hydrocarbyl;
- R4 is selected from the group consisting of hydrogen, acyl, trialkylsilyl, tertiary-alkyl, aryl-substituted methyl, and alkoxy-carbonyl;
- R6 is a substituent at C5 or C7 and is selected from hydrogen, alkyl, and acyl;
- and,
- the dashed bond between carbon atoms C7 and C8 indicates the optional presence of a carbon-carbon double bond;
- the process comprising contacting the compound of formula (III) with a super acid under process conditions suitable for forming a bond between the oxygen atom of the —OR4 substituent of the A ring and a carbon atom of the C ring to form a furan ring.
A process for making a compound of Formula (VI):
- wherein:
- R1 and R2 are independently selected from the group consisting of hydrogen, halogen, alkoxy, cyano, hydrocarbyl, substituted hydrocarbyl and NRcRd, wherein each of Rc and Rd are independently selected from the group consisting of hydrogen hydroxy and hydrocarbyl;
- R3 and R5 are independently selected from the group consisting of hydrogen, hydrocarbyl and substituted hydrocarbyl;
- R4 is selected from the group consisting of hydrogen, acyl, trialkylsilyl, tertiary-alkyl, aryl-substituted methyl and alkoxy carbonyl;
- and,
- R6 is a substituent at C5 or C7 and is selected from H or CH3;
- the process comprising contacting a compound of Formula (V) with a super acid under process conditions suitable for forming a bond between the oxygen atom of the —OR4 substituent of the A ring and a carbon atom of the C ring to form a furan ring.
Dependencies are inferred from the claim text.