Process for preparation of phenyl carbamate derivatives
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Publication Number
US-8859817-B2
Publication Date
2014-10-14
Expiration Date
Abstract
Provided are a process for the preparation of phenyl carbamate derivatives, useful in the treatment of CNS (central nervous system) disorders, an intermediate in the synthesis of the phenyl carbamate derivatives, and a process for preparation of the intermediate.
Core Innovation
The invention relates to a process for the preparation of a compound of Chemical Formula 1 by performing a carbamation of a compound of Chemical Formula 6. The carbamation is carried out by reacting the compound of Chemical Formula 6 with chlorosulfonyl isocyanate to produce a phenyl carbamate compound of Chemical Formula 1, wherein X is one or more independently selected from halogens, n is an integer from 1 to 5, and R1 is selected from a linear or branched alkyl group having 1-10 carbon atoms.
The disclosure also provides a process for deprotecting a protected carbamate compound of Chemical Formula 9 to produce the phenyl carbamate compound of Chemical Formula 1. A process of preparing a compound of Chemical Formula 6 is described by protecting a diol compound of Chemical Formula 5 by introducing a protecting group into the diol compound. The protecting group is an alcohol-protecting group selected from trialkyl silyl group, ether group, and benzoyl group.
The invention further describes preparation examples for trans alkene compounds and chiral vicinal diols bearing dichlorophenyl substituents with varying side-chain structures and halogen patterns. The examples include conversion to chiral vicinal diols with (S,S) and (R,R) stereochemistry, and the document notes selectivity for single carbamate regioisomers and productivity/cost advantages.
Claims Coverage
The independent claims cover three process families and multiple formula-defined intermediates. Across the claims, the inventive features include carbamation of Chemical Formula 6 with chlorosulfonyl isocyanate to obtain Chemical Formula 1, deprotection of protected carbamate Chemical Formula 9 to Chemical Formula 1, protection of Chemical Formula 5 to form Chemical Formula 6, and compound claims for Chemical Formulas 6, 7, 8, and 9 with halogen, n, R1, and alcohol-protecting group limitations.
Carbamation with chlorosulfonyl isocyanate to phenyl carbamate of Chemical Formula 1
A process of the preparation of a compound of Chemical Formula 1 comprising performing a carbamation of a compound of Chemical Formula 6 by reacting the compound of Chemical Formula 6 with chlorosulfonyl isocyanate to produce a phenyl carbamate compound of Chemical Formula 1, wherein X is one or more independently selected from halogens, n is an integer from 1 to 5, and R1 is selected from a linear or branched alkyl group having 1-10 carbon atoms.
Deprotecting a protected carbamate compound to phenyl carbamate of Chemical Formula 1
A process of the preparation of a compound of Chemical Formula 1 comprising deprotecting a protected carbamate compound of Chemical Formula 9 to produce a phenyl carbamate compound of Chemical Formula 1, wherein X is one or more independently selected from halogens, n is an integer from 1 to 5, and R1 is selected from a linear or branched alkyl group having 1-10 carbon atoms.
Diol protection to form Chemical Formula 6
A process of the preparation of a compound of Chemical Formula 6 comprising the step of protecting a diol compound of Chemical Formula 5 by introducing a protecting group into the diol compound, to produce the compound of Chemical Formula 6, wherein X is one or more independently selected from halogens, n is an integer from 1 to 5, and R1 is selected from a linear or branched alkyl group having 1-10 carbon atoms.
Chemical Formula 6 with an alcohol-protecting group
A compound represented by Chemical Formula 6 wherein X is one or more independently selected from halogens, n is an integer from 1 to 5, R1 is selected from a linear or branched alkyl group having 1-10 carbon atoms, and the protecting group is an alcohol-protecting group selected from trialkyl silyl group, ether group, and benzoyl group.
Chemical Formula 7 with specified alcohol-protecting group category
A compound represented by Chemical Formula 7 wherein X is one or more independently selected from halogens, n is an integer from 1 to 5, R1 is selected from a linear or branched alkyl group having 1-10 carbon atoms, and the protecting group is an alcohol-protecting group selected from trialkyl silyl group, ether group, and benzoyl group.
Chemical Formula 8 with specified alcohol-protecting group category
A compound represented by Chemical Formula 8 wherein X is one or more independently selected from halogens, n is an integer from 1 to 5, R1 is selected from a linear or branched alkyl group having 1-10 carbon atoms, and the protecting group is an alcohol-protecting group selected from trialkyl silyl group, ether group, and benzoyl group.
Chemical Formula 9 defined by halogen and alkyl substitution
A compound represented by Chemical Formula 9 wherein X is one or more independently selected from halogens, n is an integer from 1 to 5, and R1 is selected from a linear or branched alkyl group having 1-10 carbon atoms.
The claims collectively cover preparing phenyl carbamate Chemical Formula 1 by carbamation from Chemical Formula 6 using chlorosulfonyl isocyanate, and by deprotecting protected carbamate Chemical Formula 9. The claim set also covers protection of diol Chemical Formula 5 to Chemical Formula 6 and formula-defined intermediates 6 through 9 with halogen substitution, alkyl substitution, and specified alcohol-protecting groups.
Stated Advantages
Low-toxicity.
Productivity/cost advantages.
Selectivity for single carbamate regioisomers.
Documented Applications
Use of phenyl carbamate derivatives as CNS-active agents for muscle relaxation, including compounds of Chemical Formula 1 defined by X, n, and R1.
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