Method for preparing (3S,4S)-4-((R)-2-(benzyloxy)tridecyl)-3-hexyl-2-oxetanone and novel intermediate used therefor
View Patent ↗The present invention relates to a high-yield method for preparing highly pure (3S,4S)-4-((R)-2-(benzyloxy)tridecyl)-3-hexyl-2-oxetanone using a metal salt of (2S,3S,5R)-2-hexyl-3,5-dihydroxyhexadecanoic acid as an intermediate.
1. A method for preparing (3S,4S)-4-((R)-2-(benzyloxy)tridecyl)-3-hexyl-2-oxetanone of formula I comprising
1) treating the compound of formula IV with a metal hydroxide in a solvent to prepare a compound of formula III;
2) treating the compound of formula III with a bezylation reagent in a solvent in the presence of a base to prepare the compound of formula II; and
3) subjecting the compound of formula II to a cyclization reaction to obtain the compound of formula I:
wherein,
M is Na, K, or Li.
2. The method of claim 1 , wherein the solvent used in step 1 ) is an aprotic solvent selected from the group consisting of diethyl ether, methyl t-butyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, acetonitrile, methyl acetate, ethyl acetate, toluene and a mixture thereof, or a mixture of the aprotic solvent and water.
3. The method of claim 1 , wherein the metal hydroxide in step 1 ) is used in an amount of 1 to 50 mole equivalents based on the compound of formula IV.
4. The method of claim 1 , wherein the solvent used in step 2 ) is an aprotic solvent selected from the group consisting of tetrahydrofuran, diethyl ether, methyl t-butyl ether, 1,2-dimethoxyethane, 1,4-dioxane, dichloromethane, dichloroethane, acetonitrile, methyl acetate, ethyl acetate, toluene, N,N-dimethylformimide, dimethyl sulfoxide and a mixture thereof, or a mixture of the aprotic solvent and water.
5. The method of claim 1 , wherein the base used in step 2 ) is selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium t-butoxide, sodium t-butoxide, and potassium t-butoxide.
6. The method of claim 5 , wherein the base is used in an amount of 1 to 5 mole equivalents based on the compound of formula III.
7. The method of claim 1 , wherein the benzylation reagent used in step 2 ) is benzyl halide selected from the group consisting of benzyl chloride, benzyl bromide, and benzyl iodide.
8. The method of claim 1 , wherein the benzylation reagent in step 2 ) is used in an amount of 1 to 5 mole equivalents based on the compound of formula III.
9. A compound of formula III:
wherein,
M is Na, K, or Li.
10. A method for preparing the compound of formula III comprising the step of treating (3S,4S,6R)-3-hexyl-4-hydroxy-6-undecyltetrahydropyran-2-one of formula IV with a metal hydroxide in a solvent:
wherein,
M is Na, K, or Li.
11. A method for preparing the compound of formula II comprising the step of treating a metal salt of (2S,3S,5R)-3,5-dihydroxy-2-hexyl-hexadecanoic acid of formula III with a bezylation reagent in a solvent in the presence of a base:
wherein,
M is Na, K, or Li.