Synthesis of spiro esters, spiro ortho carbonates, and intermediates
AssigneeBioavailability Systems, LLC
InventorsRobert Seemayer, Jack Liang
Life of this patent
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Abstract
Ortho esters and ortho carbonates can be produced by alkylating esters and carbonates with, for example, the hexafluorophosphate salt of a trialkyl oxonium ion. The spiro species are useful intermediates in the synthesis of complex organic molecules. Synthetic pathways for the production of medically active compounds incorporates spiro ortho esters. Anti-first-pass effect materials are produced in high yield utilizing a synthetic strategy incorporating cyclic ortho ester intermediates.
Claims33
A process for the synthesis of an ortho ester or ortho carbonate comprising reacting an ester or carbonate with an agent that comprises a tri C1-20 alkyl oxonium ion and an anion of a fluorinated main group element other than [Et3O] [BF4].
A process for the synthesis of an ortho ester or ortho carbonate from a hydroxy functionalized ester comprising reacting the hydroxy functionalized ester with a protecting group to form a protected hydroxyl ester, followed by reacting said protected hydroxyl ester with an agent, wherein said agent comprises a tri C1-20 alkyl oxonium ion and an anion of a fluorinated main group element and does not comprise [Et3O] [BF4].
A process for the synthesis of an orthoester or orthocarbonate comprising:
- reacting an ester or carbonate with a trialkyloxonium alkylating agent comprising a group V hexafluoride anion to form an alkylated ester cation or alkylated carbonate cation, and
- reacting the alkylated ester cation or alkylated carbonate cation with an alkoxide salt to form the orthoester or orthocarbonate.
A process for synthesis of an ortho ester of a hydroxyl-functionalized ester comprising:
- reacting the hydroxyl-functionalized ester with a hydroxyl-protecting reagent to form a protected-hydroxyl functionalized ester,
- reacting the protected-hydroxyl-functionalized ester with a trialkyloxonium alkylating agent comprising a group V hexafluoride anion to form a protected-hydroxyl-functionalized alkylated ester cation,
- reacting the protected-hydroxyl-functionalized alkylated ester cation with an alkoxide salt to form a protected-hydroxyl-functionalized ortho ester, and,
- deprotecting the protected-hydroxyl-functionalized ortho ester to form the ortho ester of the hydroxyl-functionalized ester.
A process for the synthesis of a spiro orthoester comprising:
- reacting a lactone with a trialkyloxonium alkylating agent comprising a group V hexafluoride anion to form an alkylated lactone cation,
- reacting the alkylated lactone cation with an alkoxide salt to form a cyclic orthoester, and
- reacting the cyclic orthoester with a diol to form the spiro orthoester.
A process for synthesis of a spiro ortho ester of a hydroxyl-functionalized lactone comprising:
- reacting the hydroxyl-functionalized lactone with a hydroxyl-protecting reagent to form a protected-hydroxyl functionalized lactone,
- reacting the protected-hydroxyl-functionalized lactone with a trialkyloxonium alkylating agent comprising a group V hexafluoride anion to form a protected-hydroxyl-functionalized alkylated lactone cation,
- reacting the protected-hydroxyl-functionalized alkylated lactone cation with an alkoxide salt to form a protected-hydroxyl-functionalized cyclic ortho ester,
- reacting the protected-hydroxyl-functionalized cyclic ortho ester with a diol to form a protected-hydroxyl-functionalized spiro ortho ester, and
- deprotecting the protected-hydroxyl-functionalized spiro ortho ester to form the spiro ortho ester of the hydroxyl-functionalized lactone.
Dependencies are inferred from the claim text.