6-Benzyloxyindole-3-carboxaldehyde

N, N-Dimethylformamide (“DMF, ” 75 mL) was added to a three-neck round bottomed flask equipped with a nitrogen inlet and thermocouple. The flask was cooled to an internal temperature of +2.8 °C with an ice water bath. Phosphorous (V) oxychloride (12.7 mL, 137.2mmol, 1.25 equiv.) was added dropwise, keeping the internal temperature below 5 °C (1 h). Once the addition was complete, 6-benzyloxyindole 1 (25.0 g, 109.7 mmol, 1.0 equiv.) was added in 1 g portions, keeping the internal temperature below 5 °C (1 h). The dark solution was warmed to room temperature (“RT”) and held there for 1 h. A solution of sodium hydroxide (50 g) in water (250 mL) was prepared in a Morton flask and cooled to an internal temperature of2.0 °C. The dark reaction mixture was slowly added to the cold sodium hydroxide solution under vigorous stirring, keeping the internal temperature between 20—30 °C. A light beige solid separated (final pH 14). The slurry was heated slowly to an internal temperature of 70 °C and held for 10-15 mm under a light nitrogen sweep to remove evolving dimethylamine, then heated to an internal temperature of 90 °C and held there for 15 mm. Upon cooling to RT, the slurrywas diluted with water (40 mL) and the solids were collected via filtration. The filter cake was washed with water (2 x 100 mL) and dried in a vacuum oven at 50 °C and 23 Hg pressure with a slight nitrogen sweep to constant weight, affording indole aldehyde 2 (27.3 g) as a beige/tan solid. The product was used without further purification and was ground to a fine powder, if clumpy, before use in the next step.‘H NMR (400 MHz, DMSO-d6) ö::1 1.94 (br, s), 9.87 (s, 1H), 8.15 (s, 1H), 7.96 (d, J=8.5 Hz, 1H), 7.47 (d, J=7.2 Hz, 2H), 7.40 (app t, J=7.4 Hz, 2H), 7.33 (t, J7.0 Hz, 1H), 7.08 (s, 1H), 6.95 (d, J=8.5 Hz, 1H), 5.15 (s, 2H)‘3C NMR (101 MHz, DMSO-d6) ö:184.7, 155.7, 137.9, 137.8, 137.2, 128.4, 127.7, 127.6, 121.4, 118.25, 118.23, 112.4, 96.9, 69.5IR(KBr)(cm’):1634(s), 1526(m), 1426(m), 1385(m), 1159(m) HRMS (ESI) (m/z):Calc. for C16H13N02 [M+Hf: 252.1019. Found: 252.1025

Molecular Weight:251.28
XLogP3:3.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:4
Exact Mass:251.094628657
Monoisotopic Mass:251.094628657
Topological Polar Surface Area:42.1
Heavy Atom Count:19
Complexity:301
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes