Hydrochloric Acid → Indole

Temperature

2.5 °C

In a 5-L cylindrical reactor, 3 N HCl (750 mL) was added to the eutomer cinchonidine salt (256 g, 0.485 mol) in isopropyl acetate (1.5 L) at 20-25° C. The mixture was stirred for 10-15 min then separated into two layers. The isopropyl acetate layer was set aside. The lower aqueous layer was extracted with isopropyl acetate (250 mL). The combined isopropyl acetate layers were with H2O (750 mL). Heptane (1.75 L) was added to the isopropyl acetate layer then the isopropyl acetate and heptane solution (3.7 L) was distilled under atmospheric pressure to ˜¼ its original volume, approximate 1.0 L. Heptane (1 L) was added over 15-20 min at 85-90° C. then the mixture cooled to 0-5° C. over 1-2 h. The mixture was stirred at 0-5° C. for 1-2 h then filtered through a Buchner funnel lined with polypropylene cloth. The solid was washed with heptane (2×150 mL) then the product dried under vacuum under a bed of N2 for 14 h to give 89.6 g (29.9% overall yield from racemic acid) of the eutomer indole acid as an off-white solid.

1. customthen separated into two layers
2. extractionThe lower aqueous layer was extracted with isopropyl acetate (250 mL)
3. additionHeptane (1.75 L) was added to the isopropyl acetate layer
4. distillationthe isopropyl acetate and heptane solution (3.7 L) was distilled under atmospheric pressure
5. additionHeptane (1 L) was added over 15-20 min at 85-90° C.
6. stirringThe mixture was stirred at 0-5° C. for 1-2 h
7. filtrationthen filtered through a Buchner funnel
8. washThe solid was washed with heptane (2×150 mL)
9. dry with materialthe product dried under vacuum under a bed of N2 for 14 h

ORD record

ord-5f37afcf5db74aac824c1be051bfbb12

Source dataset

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07297704B2