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US 11,518,726 B2Granted
Synthesis of bicyclo[2.2.2]octane derivatives
AssigneeEastman Chemical Company
InventorsYue Rachel Hu, Robert Thomas Hembre, Gerald Charles Tustin, Zhufang Liu, Steven J. Adams
Life of this patent
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Abstract
Provided is a process for the preparation of certain 1,4-bicyclo[2.2.2]octane derivatives. The new synthetic procedure involves treating 1,4-dimethylene cyclohexane with an oxidizing agent in the presence of a transition metal catalyst to afford an oxo-substituted bicyclo[2.2.2]octane species. This intermediate structure can then be further derivatized. The processes of this disclosure thus affords a novel and simplified means for the commercial production of a wide variety of bicyclo[2.2.2]octane derivatives.
Claims18
A process comprising contacting a compound of the formula
- with (i) a transition metal catalyst comprising a palladium compound and (ii) an oxidizing agent;
- optionally in the presence of at least one of
- (I) a compound of the formula
- wherein R is chosen from hydrogen;
- and C1-C12 alkyl, optionally substituted by one or more of groups chosen from C1-C6 alkoxy, halo, nitro, and cyano;
- and wherein R* is chosen from hydrogen;
- C1-C12 alkyl, optionally substituted by one or more of groups chosen from C1-C6 alkoxy, halo, nitro, and cyano;
- and an alkali metal cation;
- or
- (II) a compound having at least one C1-C12 alkanoyloxy moiety of the formula
- wherein R is chosen from C1-C12 alkyl, optionally substituted by one or more of groups chosen from C1-C6 alkoxy, halo, nitro, and cyano;
- to afford a compound of the formula
- wherein each R1 is independently hydrogen or a group of the formula
- wherein R is C1-C12 alkyl, optionally substituted by one or more of groups chosen from C1-C6 alkoxy, halo, nitro, and cyano;
- further comprising a step chosen from (a), (b), or (c):
- (a) the step of reaction with carbon monoxide in the presence of a strong acid, followed by quenching with at least one of (i) water or (ii) an alcohol of the formula R—OH, to afford compounds of the formula
- wherein R is chosen from hydrogen;
- and C1-C12 alkyl, optionally substituted by one or more of groups chosen from C1-C6 alkoxy, halo, nitro, and cyano;
- optionally further comprising the step of:
- contacting with hydrogen in the presence of a heterogeneous copper hydrogenation catalyst or a homogeneous hydrogenation catalyst to afford a compound of the formula
- optionally followed by reductive amination to afford a compound of the formula
- (b) the step of conversion to a compound of the formula:
- which comprises reaction of (I) with a nitrile in the presence of an acid followed by hydrolysis to the corresponding amine;
- optionally further comprising treatment of said corresponding amine with phosgene (COCl2) to afford a compound of the formula:
- or
- (c) the step of halogenation of (I) to afford a compound of the formula:
- wherein X is halo;
- optionally further comprising a step chosen from:
- a. reaction with carbon monoxide in the presence of a strong acid, followed by quenching with at least one of (i) water or (ii) an alcohol of the formula R—OH, to afford compounds of the formula
- wherein R is chosen from hydrogen;
- and C1-C12 alkyl, optionally substituted by one or more of groups chosen from C1-C6 alkoxy, halo, nitro, and cyano;
- b. amination via treatment with ammonia to afford a compound of the formula:
- or
- b. hydroformylation via treatment with carbon monoxide and hydrogen in the presence of at least one of a cobalt or ruthenium catalyst at a temperature of about 90 to 250° C. and a pressure of about 5 to 300 bar, to afford a compound of the formula:
- optionally further comprising:
- a. treatment with an oxidizing agent, optionally in the presence of a homogeneous and/or heterogeneous catalyst to afford a compound of the formula:
- or
- b. hydrogenation in the presence of a homogeneous and/or heterogeneous catalyst to afford a compound of the formula:
35 more elements
A process for preparing a compound of the formula
- wherein R is independently hydrogen;
- or C1-C12 alkyl, optionally substituted by one or more of groups chosen from C1-C6 alkoxy, halo, nitro, and cyano;
- or phenyl, optionally substituted by one or more of groups chosen from C1-C6 alkoxy, halo, nitro, cyano, and C1-C12 alkyl;
- which comprises reaction of the compound of the formula
- wherein each R1 is independently hydrogen or a group of the formula
- wherein R is independently hydrogen;
- or C1-C12 alkyl, optionally substituted by one or more of groups chosen from C1-C6 alkoxy, halo, nitro, and cyano;
- or phenyl, optionally substituted by one or more of groups chosen from C1-C6 alkoxy, halo, nitro, cyano, and C1-C12 alkyl;
- with carbon monoxide in the presence of a strong acid, followed by quenching with at least one of (i) water or (ii) an alcohol of the formula R—OH;
- wherein R is independently hydrogen;
- or C1-C12 alkyl, optionally substituted by one or more of groups chosen from C1-C6 alkoxy, halo, nitro, and cyano;
- or phenyl, optionally substituted by one or more of groups chosen from C1-C6 alkoxy, halo, nitro, cyano, and C1-C12 alkyl.
9 more elements
A process for preparing a compound of the formula
- which comprises contacting a compound of the formula
- wherein R is C1-C6 alkyl, with hydrogen in the presence of a homogeneous ruthenium catalyst.
A process for preparing a compound of the formula
- which comprises subjecting a compound of the formula:
- to reductive amination.
A process for preparing a compound of the formula
- which comprises contacting a compound of the formula
- wherein R is chosen from hydrogen;
- and C1-C12 alkyl, optionally substituted by one or more of groups chosen from C1-C6 alkoxy, halo, nitro, and cyano;
- with hydrogen in the presence of a homogeneous hydrogenation catalyst.
1 more element
Dependencies are inferred from the claim text.