(R)-(2-methyloxiran-2-yl)methyl 4-bromobenzenesulfonate

Patent metadata

Field	Value
Publication number	US-11958818-B2
Application number	US-202017607429-A
Country	US
Kind code	B2
Filing date	Apr 29, 2020
Priority date	May 1, 2019
Publication date	Apr 16, 2024
Grant date	Apr 16, 2024

Abstract

The present invention relates to compound of formula (I), wherein R1 is chloro, bromo iodo or a brosylate group. The present invention also relates to methods of making this compound and its use in carrying out organic transformations.

First claim

What is claimed is:

1. A process for making Compound 1:

the process comprising:
(i) contacting an admixture comprising methylallyl alcohol, (+)-di-isopropyl L-tartrate (L-DIPT) and a solvent/diluent with molecular sieves to provide a first anhydrous admixture;
(ii) cooling the first anhydrous admixture;
(iii) adding Ti(O-iPr) 4 to the cooled anhydrous admixture in step (ii) to provide a second anhydrous admixture;
(iv) adding cumene hydroperoxide to the second anhydrous admixture of step (iii) to provide a first reaction mixture;
(v) allowing the contents of the first reaction mixture to react to provide an admixture comprising INT-1;

(vi) filtering the admixture obtained from step (v) to provide a filtrate comprising INT-1;
(vii) optionally treating the filtrate obtained from step (vi) with trimethylphosphite to quench unreacted cumene hydroperoxide (“the quenched filtrate”); and
(viii) treating the filtrate from step (vi) or the optionally quenched filtrate of step (vii) with triethylamine (Et 3 N), 4-dimethylaminopyridine (DMAP), and 4-bromobenzene-1-sulfonyl chloride (BrsCl) to provide a second reaction mixture; and
(ix) allowing the contents of the second reaction mixture to react to provide an admixture comprising Compound 1.

2. The process of claim 1 , wherein the molecular sieves used in step (i) of the water scavenger process is 4 Å molecular sieves.

3. The process of claim 1 , wherein the solvent/diluent used in step (i) of the water scavenger process is methylene chloride or toluene.

4. The process of claim 1 , wherein the solvent/diluent used in step (i) of the water scavenger process is methylene chloride or toluene.

5. The process of claim 1 , further comprising:
(x) isolating Compound 1 from the admixture of step (ix).

6. A process for making Compound 1

the process comprising:
(i) carrying out an azeotropic distillation of solution comprising cumene hydroperoxide and a solvent capable of forming an azeotrope to provide a first anhydrous solution;
(ii) cooling the first anhydrous solution;
(iii) carrying out an azeotropic distillation of a solution comprising methylallyl alcohol, (+)-di-isopropyl L-tartrate (L-DIPT), and a solvent capable of forming an azeotrope to provide a second anhydrous solution;
(iv) cooling the second anhydrous solution;
(v) adding titanium tetraisoproxide (Ti(O-iPr) 4 ) to the cooled second anhydrous solution in step (iv);
(vi) combining the cooled first solution from step (ii) with the cooled second anhydrous solution from step (v) to provide a first reaction solution;
(vii) allowing the contents of the first reaction solution from step (vi) to react to provide a solution comprising INT-1;
(viii) optionally treating the solution obtained from step (vii) with trimethylphosphite to quench unreacted cumene hydroperoxide; and
(ix) treating the solution obtained from step (vii), or the optionally quenched solution of step (viii), with triethylamine (Et 3 N), 4-dimethylaminopyridine (DMAP), and 4-bromobenzene-1-sulfonyl chloride (BrsCl) to provide a reaction solution comprising Compound 1.

7. The process of claim 6 , wherein the solvent capable of forming an azeotrope used in step (i) and step (iii) is methylene chloride or toluene.

8. The process of claim 6 , further comprising:
(x) isolating Compound 1 from the reaction solution of step (ix).

9. A process for making the compound of formula I

wherein R 1 is chloro, bromo, or iodo,
the process comprising reacting Compound 1 of formula:

with a tetraethylammonium halide of formula (CH 3 CH 2 ) 4 N + X − in a suitable diluent/solvent,
wherein X is chloro, bromo, or iodo.

10. The process of claim 9 , wherein X is iodo and the product is Compound 2

11. The process of claim 9 , wherein the suitable diluent/solvent is dimethylformamide.

Assignees

• Boehringer Ingelheim Int

Inventors

• Patel Nitinchandra D

Classifications

• C07D301/19 Primary

  with organic hydroperoxides · CPC title

• C07D303/08

  with hydrocarbon radicals, substituted by halogen atoms, nitro radicals or nitroso radicals · CPC title

• C07D303/16

  by esterified hydroxyl radicals · CPC title