Toluene diisocyanate manufacturer Knowledge Preparation method of 2,4-dichloro-6-fluorobenzaldehyde_Kain Industrial Additive

Preparation method of 2,4-dichloro-6-fluorobenzaldehyde_Kain Industrial Additive

Background and overview[1]

2,4-Dichloro-6-fluorobenzaldehyde can be used as a pharmaceutical synthesis intermediate.

Preparation[1]

The preparation of 2,4-dichloro-6-fluorobenzaldehyde is as follows:

To a solution of 1,3-dichloro-5-fluorobenzene (2.0g, 12mmol) in tetrahydrofuran (20mL) at -70°C, lithium diisopropylamide (2M solution in tetrahydrofuran, 18mmol) was added dropwise. 9.1mL). The reaction was stirred at -70 °C for 0.5 h, then N,N-dimethylformamide (1.8 g, 24 mmol) was slowly added and stirring was continued at -70 °C for 0.5 h. The reaction was quenched with water (20 mL) and extracted with ethyl acetate (3 x 20 mL). The combined organic layers were concentrated in vacuo and purified by silica gel chromatography [petroleum ether: ethyl acetate = 30:1] to obtain 2,4-dichloro-6-fluorobenzaldehyde (1.5g, 64% yield), It is a yellow solid. 1H-NMR (CDCl3, 400MHz): 510.41 (s, 1H), 7.934 (s, 1H), 7.18-7.16 (d, J=10.0Hz, 1H).

Application

2,4-Dichloro-6-fluorobenzaldehyde can be used as a pharmaceutical synthesis intermediate. If the following reaction occurs:

1) Dissolve 2,4-dichloro-6-fluorobenzaldehyde (1eq), hydroxylamine hydrochloride (1.3-2 eq.) and triethylamine (2eq.) in dichloromethane (1.2-2.5mL/mmol aldehyde ) was stirred at room temperature for 16 hours. Upon completion, the reaction mixture was diluted with water and extracted with dichloromethane (3 × 20 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give the oxime intermediate. The intermediate was purified by silica gel chromatography or used in the next step without further purification.

2) To a solution of the oxime intermediate (1 equiv) in dichloromethane (10 mL) at 0°C, add N-chlorosuccinimide (1.2 equiv) in N,N-dimethylformamide (0.5mL) solution. The mixture was stirred at 30°C for 1 hour. Upon completion, the reaction mixture was diluted with water and extracted with dichloromethane (3 × 10 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give the N-hydroxyimidyl chloride intermediate.

Main reference materials

[1](WO2016201096)AMINOBENZISOXAZOLECOMPOUNDSASAGONISTSOFA7-NICOTINICACETYLCHOLINERECEPTORS

This article is from the Internet, does not represent the position of Toluene diisocyanate reproduced please specify the source.https://www.chemicalchem.com/archives/2289

author:

Previous article
Next article
Contact Us

Contact us

+86 - 152 2121 6908

Online consultation: QQ交谈

E-mail: sales@newtopchem.com

Working hours: Monday to Friday, 9:00-17:30, closed on holidays
Follow wechat
Scan wechat and follow us

Scan wechat and follow us

Follow Weibo
Back to top
Home
E-mail
Products
Search