Potassium Carbonate → N-Amino-3-chloro-1H-indole

Temperature

0 °C

To a 12 L round bottom flask equipped with a mechanical stirrer, thermometer and a Gooch tube was added sieve-dried dimethylformamide (2.8 L), 3-chloroindole (240 g, 91.6% pure), milled potassium carbonate (200.4 g), milled potassium hydroxide (574.3 g, 85% pure) and dimethylformamide (900 mL) at −2° to 5° C. The reaction mixture was cooled to about 0° C. and hydroxylamine-O-sulfonic acid (338.2 g, 97% pure) was added portionwise via the Gooch tube over a period of about 4 hrs, maintaining the reaction temperature at about 0° C. When the reaction was >95% complete (by high performance liquid chromatography), the reaction mixture was poured into a well-stirred, cold mixture of water (18 L and 3.6 kg ice) and toluene (2.4 L). After about 5 mins, the phases were separated and the aqueous phase was extracted with toluene (1×2.4 L and 1×1 L). The organic fractions were combined and filtered through Celite. The filtrate was concentrated under reduced pressure (about 50 mm Hg) at about 60° C. to yield 245 g (86%) of product.

1. customTo a 12 L round bottom flask equipped with a mechanical stirrer
2. temperaturemaintaining the reaction temperature at about 0° C
3. customthe phases were separated
4. extractionthe aqueous phase was extracted with toluene (1×2.4 L and 1×1 L)
5. filtrationfiltered through Celite
6. concentrationThe filtrate was concentrated under reduced pressure (about 50 mm Hg) at about 60° C.

ORD record

ord-dcdb0d9fe2b2467abf27c436edabac20

Source dataset

uspto-grants-2003_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06512125B1