Bis(2-chloroethyl) ether → 4-(1H-Indol-6-yl)morpholine

Temperature

100 °C

A mixture of 1H-indol-6-amine (3.14 g, 23.76 mmol), 1-chloro-2-(2-chloroethoxy)ethane (4.18 mL, 35.6 mmol), and sodium carbonate (10.07 g, 95 mmol) in t-BuOH (90 mL) was heated at 100° C. in a pressure tube for 3.5 days. On cooling to room temperature, the mixture was diluted with ethyl acetate and filtered through CELITE®. The filtrate was concentrated under vacuum to dryness. To the residue was added water (50 mL). The mixture was adjusted to pH 11 with saturated NaHCO3 solution and extracted with CH2Cl2 (4×80 mL). The combined extract was washed with brine (50 mL) and dried over anhydrous MgSO4. The desired product (3.96 g, 19.58 mmol, 82% yield) was isolated as a beige solid with ISCO (300 g silica gel, solid loading, 20-50% ethyl acetate/hexane).

1. temperatureOn cooling to room temperature
2. filtrationfiltered through CELITE®
3. concentrationThe filtrate was concentrated under vacuum to dryness
4. additionTo the residue was added water (50 mL)
5. extractionextracted with CH2Cl2 (4×80 mL)
6. extractionThe combined extract
7. washwas washed with brine (50 mL)
8. dry with materialdried over anhydrous MgSO4

ORD record

ord-ffbb58392a274cd18784196b490dea34

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08685969B2