Preparation method of thiazole derivative

Abstract

The invention discloses a preparation method of a thiazole derivative, namely (4-(5-chlorine-2,3-dihydrobenzo[b][1,4] dioxino-6) thiazole-2) methanol. A target product is prepared by taking 3-chlorobenzene-1,2-diol as a starting material via cyclization, Friedel-Crafts reaction, cyclization, acetal protection removal and reduction. The compound is an important pharmaceutical intermediate.

Description

technical field

[0001] The invention relates to a novel preparation method of a pharmaceutical intermediate, in particular to a (4-(5-chloro-2,3-dihydrobenzo[b][1,4]dioxene-6- A kind of preparation method of the preparation method of methyl) thiazol-2-yl) methanol. technical background

[0002] Compound (4-(5-chloro-2,3-dihydrobenzo[b][1,4]dioxen-6-yl)thiazol-2-yl)methanol, the structural formula is:

[0003]

[0004] The compound (4-(5-chloro-2,3-dihydrobenzo[b][1,4]dioxen-6-yl)thiazol-2-yl)methanol and related derivatives are It is widely used in medicinal chemistry and organic synthesis. The synthesis of (4-(5-chloro-2,3-dihydrobenzo[b][1,4]dioxen-6-yl)thiazol-2-yl)methanol is currently difficult. Therefore, it is necessary to develop a synthesis method with easily available raw materials, convenient operation, easy control of the reaction and suitable overall yield. SUMMARY OF THE INVENTION

[0005] The invention discloses a method for preparing (4-(5-chloro-2,3...

Examples

Embodiment 1

[0023] (1) Synthesis of 5-chloro-2,3-dihydrobenzo[b][1,4]dioxin

[0024] Add 30g 3-chlorobenzene-1,2-diol to 400ml N,N-dimethylformamide, add 21g anhydrous potassium carbonate, then add 35g 1,2-dibromoethane, heat under reflux and stir for 15 hours , cooled to room temperature, concentrated to remove most of the N,N-dimethylformamide, added water and ethyl acetate, extracted, separated, dried, concentrated, and the residue was separated on a column to obtain 38g of 5-chloro-2,3- Dihydrobenzo[b][1,4]dioxin.

[0025] (2) Synthesis of 2-bromo-1-(5-chloro-2,3-dihydrobenzo[b][1,4]dioxen-6-yl)ethanone

[0026] 38g of 5-chloro-2,3-dihydrobenzo[b][1,4]dioxin was added to 500ml of dichloromethane, 60g of bromoacetyl bromide was added, heated to reflux for 4 hours, cooled to room temperature, and then Water was added, extracted and separated, the organic phase was collected, separated, dried and concentrated, and the residue was separated on a silica gel column to obtain 42 g of 2-bro...

technical field

[0001] The invention relates to a novel preparation method of a pharmaceutical intermediate, in particular to a (4-(5-chloro-2,3-dihydrobenzo[b][1,4]dioxene-6- A kind of preparation method of the preparation method of methyl) thiazol-2-yl) methanol. technical background

[0002] Compound (4-(5-chloro-2,3-dihydrobenzo[b][1,4]dioxen-6-yl)thiazol-2-yl)methanol, the structural formula is:

[0003]

[0004] The compound (4-(5-chloro-2,3-dihydrobenzo[b][1,4]dioxen-6-yl)thiazol-2-yl)methanol and related derivatives are It is widely used in medicinal chemistry and organic synthesis. The synthesis of (4-(5-chloro-2,3-dihydrobenzo[b][1,4]dioxen-6-yl)thiazol-2-yl)methanol is currently difficult. Therefore, it is necessary to develop a synthesis method with easily available raw materials, convenient operation, easy control of the reaction and suitable overall yield. SUMMARY OF THE INVENTION

[0005] The invention discloses a method for preparing (4-(5-chloro-2,3...

Examples

Embodiment 1

[0023] (1) Synthesis of 5-chloro-2,3-dihydrobenzo[b][1,4]dioxin

[0024] Add 30g 3-chlorobenzene-1,2-diol to 400ml N,N-dimethylformamide, add 21g anhydrous potassium carbonate, then add 35g 1,2-dibromoethane, heat under reflux and stir for 15 hours , cooled to room temperature, concentrated to remove most of the N,N-dimethylformamide, added water and ethyl acetate, extracted, separated, dried, concentrated, and the residue was separated on a column to obtain 38g of 5-chloro-2,3- Dihydrobenzo[b][1,4]dioxin.

[0025] (2) Synthesis of 2-bromo-1-(5-chloro-2,3-dihydrobenzo[b][1,4]dioxen-6-yl)ethanone

[0026] 38g of 5-chloro-2,3-dihydrobenzo[b][1,4]dioxin was added to 500ml of dichloromethane, 60g of bromoacetyl bromide was added, heated to reflux for 4 hours, cooled to room temperature, and then Water was added, extracted and separated, the organic phase was collected, separated, dried and concentrated, and the residue was separated on a silica gel column to obtain 42 g of 2-bro...

Images