Synthesis of dioxabicyclo(3.2.1)octanes and oxepanes

Claim 2

The process for the preparation of compounds of the formula: which comprises treating a hemi-ketal of the formula: with potassium acetate followed by reaction with methoxyamine hydrochloride to obtain an alcohol of the formula: reacting the alcohol with an acylating agent to obtain an ester of the formula: and treating the ester which forms with dilute acid wherein R is a straight or branched chain alkyl or alkenyl group of from 1-12 carbon atoms and R 3 is an alkanoyl group having 2-5 carbon atoms.

Claim 3

The process of Claim 1 wherein the acylating.agent is acetic anhydride. or Claim 2

Claim 4

The process of Claim 1/wherein the dilute acid is dilute hydrochloric acid.

Claim 5

A compound of the formula: wherein R 3 is hydrogen or lower alkanoyl having 2-5 carbon atoms and R 2 is lower alkanoyloxy having 2-5 carbon atoms.

Claim 6

A compound of the formula: wherein R 3 is hydrogen or lower alkanoyl having 2-5 carbon atoms and R 2 is lower alkanoyloxy having 2-5 carbon atoms.

Claim 7

The compound of Claim 4 wherein R 3 is hydrogen and R 2 is acetyloxy.

Claim 8

The compound of Claim 4 wherein R 3 is acetyl and R 2 is acetyloxy.

Claim 9

The process for the preparation of a compound of Claim 4 of the formula: which comprises reacting a compound of the formula: with an alkali metal acetate followed by reaction with methoxyamine hydrochloride wherein R 2 is lower alkanoyloxy having 2-5 carbon atoms.

Claim 10

The process of Claim 7 wherein the alkali metal acetate is potassium acetate.

Claim 11

or Claim 8 9. The process of Claim 7/wherein the lower alkanoyloxy group is an acetyloxy group.

Claim 12

The process for the preparation of a compound of - Claim 4 of the formula: which comprises reacting a compound of the formula. with an alkali metal acetate, followed by reaction with methoxyamine hydrochloride to form a compound of the formula: and reacting the alcohol with a acylating agent, wherein R 3 is lower alkanoyl having 2-5 carbon atoms and R 2 is lower alkanoyloxy having 2-5 carbon atoms.

Claim 13

The process for the preparation of compounds of the formula: which comprises reacting a compound of the formula with lithium diisopropylamide followed by reaction of the intermediate with trimethylsilyl chloride to form a silyl enol ether of the formula: . reacting the enol ether with N-bromosuccinimide to form a bromide of the formula: reacting the bromide with a peracid to form an epoxide of the formula: reacting the epoxide with an acid to form a hemi-ketal of the formula: reacting the hemi-ketal with a trialkylorthoformate to form a ketal of the formula: reacting the ketal with a cyclizing agent to form an oxido oxepane of the formula: reacting the oxido oxepane with dilute acid to give a mixture of epimeric hemi-ketals of the formula: separating the epimers by physical means and (i.) reacting Compound A with a carbalkoxymethylenetriphenylphosphorane to form an ester of the formula: and hydrolyzing the ester with a base; and (ii.) reacting Compound B with a carbalkoxymethylenetriphenylphosphorane to form an ester of the formula: and hydrolyzing the ester with a base, wherein R is a straight or branched chain alkyl group having 1 to 12 carbon atoms and R 1 and R 2 are lower alkyl having 1 to 5 carbon atoms.

Claim 14

The process for the preparation of compounds of the formula: which comprises reacting a compound of the formula with lithium diisopropylamide followed by reaction of the intermediate with trimethylsilyl chloride to form a silyl enol ether of the formula: . reacting the enol ether with N-bromosuccinimide to form a bromide of the formula: reacting the bromide with a peracid to form an epoxide of the formula: reacting the epoxide with an acid to form a hemi-ketal of the formula: reacting the hemi-ketal with a trialkylorthoformate to form a ketal of the formula: reacting the ketal with a cyclizing agent to form an oxido oxepane of the formula: reacting the oxido oxepane with dilute acid to give a mixture of epimeric hemi-ketals of the formula: separating the epimers by physical means and (i.) reacting Compound A with a carbalkoxymethylenetriphenylphosphorane to form an ester of the formula: and hydrolyzing the ester with a base; and (ii.) reacting Compound B with a carbalkoxymethylenetriphenylphosphorane to form an ester of the formula: and hydrolyzing the ester with a base, wherein R is a straight or branched chain alkyl group having 1 to 12 carbon atoms and R 1 and R 2 are lower alkyl having 1 to 5 carbon atoms.

Claim 15

The process of Claim 11 wherein the acid is hydrochloric acid.

Claim 16

The process of Claim 11 or Claim 12 wherein the cyclizing agent is potassium hydroxide.

Claim 17

The process of any one of Claims 11 to 13 wherein the carbalkoxymethylenetriphenylphosphorane is carbethoxymethylenetriphenylphosphorane.

Claim 18

The process of any one of Claims 11 to 14 wherein the base is potassium hydroxide.

Claim 19

The process according to any one of Claims 11 to 15 wherein the dilute acid is selected from hydrochloride acid, sulfuric acid and acetic acid.

Claim 20

The process of any one of Claims 11 to 16 wherein the peracid is m-chloroperbenzoic acid.

Claim 21

The process of any one of Claims 11 to 17 wherein the trialkylorthoformate is trimethylorthoformate.

Claim 22

The process for the preparation of compounds of the formula: which comprises reacting a ketal of the formula: with a cyclizing agent to form an oxido-oxepane of the formula: reacting the oxido-oxepane with dilute acid to give a mixture of epimeric hemi-ketals of the formula: separating the epimers by physical means and (i.) reacting Compound A with a carbalkoxymethylenetriphenylphosphorane to form an ester of the formula: and hydrolyzing the ester with a base; and (ii.) reacting Compound B with a carbalkoxymethylenetriphenylphosphorane to form an ester of the formula: and hydrolyzing the ester with a base, wherein R is a straight or branched chain alkyl group having 1 to 12 carbon atoms and R 1 and R 2 are lower alkyl having 1 to 5 carbon atoms.

Claim 23

The process for the preparation of compounds of the formula: which comprises reacting a ketal of the formula: with a cyclizing agent to form an oxido-oxepane of the formula: reacting the oxido-oxepane with dilute acid to give a mixture of epimeric hemi-ketals of the formula: separating the epimers by physical means and (i.) reacting Compound A with a carbalkoxymethylenetriphenylphosphorane to form an ester of the formula: and hydrolyzing the ester with a base; and (ii.) reacting Compound B with a carbalkoxymethylenetriphenylphosphorane to form an ester of the formula: and hydrolyzing the ester with a base, wherein R is a straight or branched chain alkyl group having 1 to 12 carbon atoms and R 1 and R 2 are lower alkyl having 1 to 5 carbon atoms.

Claim 24

The process of Claim 19 wherein the cyclizing agent is potassium hydroxide.

Claim 25

The process of Claim 19 or 20 wherein the carbalkoxymethylenetriphenylphosphorane is carbethoxymethylenetriphenylphosphorane.

Claim 26

The process of any one of Claims 19 to 21 wherein the base is sodium hydroxide.

Claim 27

The process of any one of Claims 19 to 22 wherein the dilute acid is selected from hydrochloric acid, sulfuric acid and acetic acid.