Ammonium Chloride → Ethyl 4-bromo-1H-indole-2-carboxylate

Temperature

7.5 °C

A solution of 23 mL of ethyl azidoacetate and 7.6 mL of 2-bromobenzaldehyde in 40 mL ethanol was added dropwise to a solution of 4.5 g sodium in 180 mL ethanol, in a bath at −10° C., at a rate such that the reaction temperature does not rise above 8° C. After the addition is complete, the mixture is stirred at 5-10° C. for 30 min. The reaction mixture is then poured into a mixture of 28 g of NH4Cl in 1 L ice, and extracted with 1:4 CH2Cl2hexane. The organic phase is filtered through 150 mL silica gel, which is rinsed with 200 mL of the same solvent. This is evaporated to near dryness, diluted with 300 mL xylene, and stabilised with 60 mg of 2,5-di-t-butylhydroquinone. This mixture is heated with a distillation head until 50 mL of xylene has distilled. The mixture is cooled and evaporated in vacuo to a volume of 80 mL, which is diluted with 80 mL of hexane. A white solid forms upon cooling to 0° C., which is filtered off.

1. customdoes not rise above 8° C
2. additionAfter the addition
3. extractionextracted with 1:4 CH2Cl2hexane
4. filtrationThe organic phase is filtered through 150 mL silica gel, which
5. washis rinsed with 200 mL of the same solvent
6. customThis is evaporated
7. additiondiluted with 300 mL xylene
8. temperatureThis mixture is heated with a distillation head until 50 mL of xylene
9. distillationhas distilled
10. temperatureThe mixture is cooled
11. customevaporated in vacuo to a volume of 80 mL, which
12. additionis diluted with 80 mL of hexane
13. temperatureA white solid forms upon cooling to 0° C.
14. filtrationwhich is filtered off

ORD record

ord-ef6a03371bc9449d9a2480416cbd63ce

Source dataset

uspto-grants-2002_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06436965B1