Sodium Hydroxide → 6-cyano-1H-indole-2-carboxylic Acid

A solution of 4-cyanobenzaldehyde (1.27 g, 9.69 mmol) and ethyl azidoacetate (5 g, 38.76 mmol) in methanol (6 ml) was added dropwise over 0.16 h to a stirred solution of sodium methoxide (2.143 g, 39.7 mmol) in methanol (24 ml) at −8° C. The reaction was stirred with ice cooling for a further 3 h before being poured into ice/water (500 ml). The precipitate was filtered, washed with water and dried in vacuo. A sample of the residue (0.55 g) was dissolved in xylene (15 ml) and added dropwise to refluxing xylene (35 ml) over 0.75 h. After a further 1.5 h reflux the mixture was cooled and the precipitate filtered, washed with a small amount of xylene and dried in vacuo. The residue was dissolved in aqueous methanol (20 ml, 1:1) and sodium hydroxide (1 equivalent) added. The mixture was stirred at room temperature for 18 h, concentrated to half volume and poured into water (50 ml). The resultant solution was washed with ethyl acetate (50 ml) and the aqueous layer acidified with 2N HCl. The precipitate was filtered, washed with water and dried in vacuo to afford the title compound as a pale yellow solid (0.209 g, 11%).

1. filtrationThe precipitate was filtered
2. washwashed with water
3. customdried in vacuo
4. dissolutionA sample of the residue (0.55 g) was dissolved in xylene (15 ml)
5. additionadded dropwise
6. temperatureto refluxing xylene (35 ml) over 0.75 h
7. temperatureAfter a further 1.5 h reflux the mixture
8. temperaturewas cooled
9. filtrationthe precipitate filtered
10. washwashed with a small amount of xylene
11. customdried in vacuo
12. dissolutionThe residue was dissolved in aqueous methanol (20 ml, 1:1)
13. stirringThe mixture was stirred at room temperature for 18 h
14. concentrationconcentrated to half volume
15. additionpoured into water (50 ml)
16. washThe resultant solution was washed with ethyl acetate (50 ml)
17. filtrationThe precipitate was filtered
18. washwashed with water
19. customdried in vacuo

ORD record

ord-60e4e1ef0f2243c197916cdd3cdb3097

Source dataset

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06465485B1