Processing

Please wait...

Settings

Settings

Goto Application

1. WO2020223267 - (R)-(2-METHYLOXIRAN-2-YL)METHYL 4-BROMOBENZENESULFONATE

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

Claims

What is claimed is:

1. A compound of formula I:


I

wherein R1 is chloro, bromo iodo or a brosylate group having the structure:


wherein the asterisk (*) denotes the point of attachment.

2. The compound of claim 1, wherein R1 is brosylate.

3. The compound claim 1, wherein R1 is iodo.

4. A process for making the compound of claim 2, 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(0-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 (Et3N), 4-dimethylaminopyridine (DMAP), and 4-bromobenzene-l- 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.

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

6. The process of any one of claims 4 and 5, wherein the solvent/diluent used in step (i) of the water scavenger process is methylene chloride or toluene.

7. The process of any one of claims 4 to 6, wherein the solvent/diluent used in step (i) of the water scavenger process is methylene chloride or toluene.

8. The process of any of claims 4 to 7, further comprising:

(x) isolating Compound 1 from the admixture of step (ix).

9. A process for making Compound 1 of claim 2, 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(0-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 (Et3N), 4-dimethylaminopyridine (DMAP), and 4- bromobenzene-l-sulfonyl chloride (BrsCl) to provide a reaction solution comprising Compound 1.

10. The process of claim 9, wherein the solvent capable of forming an azeotrope used in step

(i) and step (iii) is methylene chloride or toluene.

12. The process of claim 9 or 10, further comprising:

(x) isolating Compound 1 from the reaction solution of step (ix).

11. A process for making the compound of formula I of claim 1, wherein R1 is chloro, bromo or iodo, the process comprising reacting Compound 1 of formula:


1

with a tetraethylammonium halide of formula (CH3CH2)4N+X in a suitable diluent/solvent,

wherein X is chloro, bromo, or iodo.

12. The process of claim 11, wherein X is iodo and the product is Compound 2.

13. The process of claim 11 or 12, wherein the suitable diluent/solvent is

dimethylformamide .