Process for preparation of 2-Amino-5-hydroxy propiophenone

Patent metadata

Field	Value
Publication number	US-11434196-B2
Application number	US-202017419378-A
Country	US
Kind code	B2
Filing date	Jan 14, 2020
Priority date	Jan 15, 2019
Publication date	Sep 6, 2022
Grant date	Sep 6, 2022

Abstract

The present invention relates to a process for preparation of 2-Amino-5-hydroxy propiophenone, a key intermediate for the synthesis of camptothecin analogs including 7-Ethyl-10-hydroxycamptothecin (SN-38).

First claim

We claim:

1. A process for preparation of 2-amino-5-hydroxy propiophenone of Formula I,

comprising:
a) reacting a compound of Formula III with a suitable nitrating reagent to obtain a compound of Formula IV,

wherein “PG” represents a suitable hydroxyl protecting group; and
b) converting the compound of Formula IV into the 2-amino-5-hydroxy propiophenone of Formula I.

2. The process as claimed in claim 1 , wherein the hydroxyl protecting group is selected from the group consisting of trichloroethyl formate, methyl formate, ethyl formate, hexyl formate, isobutyl formate, benzyl formate, methoxymethyl, methoxyethoxymethyl, tetrahydropyranyl, tetrahydrofuran, allyl, methoxytrityl, methylthio methyl, benzyl, benzoyl, p-methoxybenzyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triisopropylsilyl, di-tert-butylsilylene, tetraisopropyldisiloxanylidene, pivaloyl, and benzoyl.

3. The process as claimed in claim 2 , wherein the hydroxyl protecting group is one of trichloroethyl formate, ethyl formate, or hexyl formate.

4. The process as claimed in claim 1 , wherein the nitrating reagent is selected from the group consisting of a nitrating mixture, sodium nitrate, potassium nitrate, calcium nitrate, cupric nitrate, and mixtures thereof, wherein the nitrating mixture is a mixture of nitric acid and sulfuric acid.

5. The process as claimed in claim 4 , wherein the nitrating reagent is one of the nitrating mixture or the potassium nitrate.

6. The process as claimed in claim 1 , wherein the step a) is carried out in a suitable solvent and optionally in the presence of an acid.

7. The process as claimed in claim 6 , wherein the solvent is selected from the group consisting of methylene chloride, ethylene chloride, chloroform, toluene, xylene, dimethyl formamide, dimethyl acetamide, dimethyl sulfoxide, N-methyl pyrrolidinone, acetonitrile, propionitrile, and mixtures thereof.

8. The process as claimed in claim 6 , wherein the acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid, phosphoric acid, acetic acid, acetic anhydride, trifluoro acetic acid, trichloro acetic acid, methane sulfonic acid, and mixtures thereof.

9. A process for preparation of 2-amino-5-hydroxy propiophenone of Formula I,

comprising:
a) reacting a compound Formula II with a suitable hydroxyl protecting agent to obtain a compound of Formula III,

wherein “PG” represents a suitable hydroxyl protecting group;
b) reacting the compound of Formula III with a suitable nitrating reagent to obtain a compound of Formula IV,

c) deprotecting the compound of Formula IV with a suitable deprotecting agent to obtain a compound of Formula V,

and
d) reducing the compound of Formula V with a suitable reducing agent to obtain 2-Amino-5-hydroxy propiophenone of Formula I or
e) reducing the compound of Formula IV with a suitable reducing agent to obtain a compound of Formula VI,

and
f) deprotecting the compound of Formula VI with a suitable deprotecting agent to obtain the 2-amino-5-hydroxy propiophenone of Formula I.

10. The process as claimed in claim 9 , wherein the hydroxyl protecting agent is selected from the group consisting of trichloroethyl chloroformate, methyl chloroformate, ethyl chloroformate, hexyl chloroformate, isobutyl chloroformate, benzylchloroformate, methoxymethylchloride, methoxyethoxy methylchloride, tetrahydropyranyl ether, allyl bromide, methoxytrityl chloride, methylthiomethyl chloride, benzyl bromide, benzoyl bromide, p-methoxybenzyl chloride, t-butyldimethylsilyl chloride, t-butyldiphenylsilyl chloride, triisopropylsilyl chloride, di-tert-butylsilylene chloride, tetraisopropyl disiloxanylidene chloride, pivaloyl chloride, and benzoyl chloride.

11. The process as claimed in claim 9 , wherein the hydroxyl protecting group is selected from the group consisting of trichloroethyl formate, methyl formate, ethyl formate, hexyl formate, isobutyl formate, benzyl formate, methoxymethyl, methoxyethoxymethyl, tetrahydropyranyl, tetrahydrofuran, allyl, methoxytrityl, methylthio methyl, benzyl, benzoyl, p-methoxybenzyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triisopropylsilyl, di-tert-butylsilylene, tetraisopropyldisiloxanylidene, pivaloyl, and benzoyl.

12. The process as claimed in claim 9 , wherein the hydroxyl protecting group is one of trichloroethyl formate, ethyl formate, or hexyl formate.

13. The process as claimed in claim 9 , wherein the hydroxyl protecting agent is one of trichloroethyl chloroformate, ethyl chloroformate, or hexyl chloroformate.

14. The process as claimed in claim 9 , wherein the step a) is carried out in presence of a suitable base and a suitable solvent.

15. The process as claimed in claim 14 , wherein the base is selected from the group consisting of sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, sodium amide, potassium amide, lithium amide, sodium methoxide, sodium ethoxide, sodium t-butoxide, potassium t-butoxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium phosphate, trisodium phosphate, potassium phosphate, tripotassium phosphate, ammonium carbonate, triethylamine, tri-n-propylamine, tri-n-butylamine, methyldibutylamine, diisopropylamine, diisopropylethylamine, dicyclohexylamine, methyl dicyclohexylamine, ethyldiisopropyl amine, N,N-diethyldicyclohexylamine, pyridine, dimethylamino-4-pyridine, N-methyl piperidine, N-ethylpiperidine, N-ethylpiperidine, N-butylpiperidine, 1,2-dimethyl piperidine, or mixtures thereof.

16. The process as claimed in claim 14 , wherein the solvent is selected from the group consisting of acetone, methyl ethyl ketone, methyl isobutyl ketone, diethyl ketone, acetonitrile, propionitrile, diethyl ether, tetrahydrofuran, methyl tetrahydrofuran, 1,4-dioxane, dimethylacetamide, dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone, methylene chloride, ethylene chloride, chloroform, toluene, xylene, water, or mixtures thereof.

17. The process as claimed in claim 9 , wherein the nitrating reagent is selected from the group consisting of nitrating mixture, sodium nitrate, potassium nitrate, calcium nitrate, cupric nitrate, and mixtures thereof, wherein the nitrating mixture is a mixture of nitric acid and sulfuric acid.

18. The process as claimed in claim 17 , wherein the nitrating reagent is the nitrating mixture or potassium nitrate.

19. The process as claimed in claim 9 , wherein the step b) is carried out in a suitable solvent optionally in presence of an acid.

20. The process as claimed in claim 19 , wherein the solvent is selected from the group consisting of methylene chloride, ethylene chloride, chloroform, toluene, xylene, dimethyl formamide, dimethyl acetamide, dimethyl sulfoxide, N-methyl pyr

Assignees

• Laurus Labs Ltd

Inventors

• Vasireddi Uma Maheswer Rao
• Kintali Venkata Ramana
• Dadi Jagadeeswara Rao
• Katkuri Raj Koti
• Tummu Sridhar

Classifications

• C07C221/00 Primary

  Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton · CPC title

• C07C201/08

  by substitution of hydrogen atoms by nitro groups · CPC title

• C07D491/147

  the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom · CPC title

• C07C201/12

  by reactions not involving the formation of nitro groups · CPC title

• C07C69/96

  Esters of carbonic or haloformic acids · CPC title