Hydrochloric Acid → 5-Cyano-3-methylthiooxindole

A solution of 4-cyanoaniline (5.0 g, 42 mmol) in dry dichloromethane (100 mL) under N2 was cooled to about −78° C. To this stirred solution was added a solution of tert-butylhypochlorite (4.6 g, 42 mmol) in dry dichloromethane (10 mL) over 5 min. and the resulting solution stirred for 10 minutes. A solution of ethyl methylthioacetate (5.45 mL, 5.69 g, 42 mmol) in dry dichloromethane (10 mL) was than added dropwise and the mixture stirred for 1 hour. Triethylamine (5.9 mL, 4.28, 42 mmol) was added dropwise and the solution allowed to warm to room temperature over 1 hour. The reaction solution was washed with water (3×20 mL) and brine (1×20 mL), dried over anhydrous MgSO4 and the solvent evaporated under vacuum to leave an orange oil. This oil was dissolved in diethyl ether (100 mL) and 2N aqueous hydrochloric acid (5 mL) was added and the mixture stirred vigorously at room temperature for 18 hours. The resulting tan solid was collected by filtration and washed with diethyl ether and dried under vacuum to give 5-cyano-3-methylthiooxindole as a white solid, (6.4 g, 76%). 1H NMR (CDCl3) δ9.04 (br s, 1H) 7.64 (s, 1H), 7.57 (d, 1H, J=8.4 Hz), 6.99 (d, 1H, J=8.4 Hz), 4.28 (s, 1H), 2.04 (s, 3H). MS (−ve ES) 203 (100), (M−H).

1. additionthan added dropwise
2. stirringthe mixture stirred for 1 hour
3. washThe reaction solution was washed with water (3×20 mL) and brine (1×20 mL)
4. dry with materialdried over anhydrous MgSO4
5. customthe solvent evaporated under vacuum
6. customto leave an orange oil
7. stirringthe mixture stirred vigorously at room temperature for 18 hours
8. filtrationThe resulting tan solid was collected by filtration
9. washwashed with diethyl ether
10. customdried under vacuum

ORD record

ord-581bd05e959c4fb48b2315c01eed55e9

Source dataset

uspto-grants-2001_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06268391B1