tert-Butanol → 2-(1-methyl-1H-indol-7-yl)acetamide

(1-Methyl-1H-indol-7-yl)-acetonitrile (adapted from the procedure described in YONEDA, R.; HARUSAWA, S.; KURIHARA, T. Tetrahedron Lett. 1989, 30, 3681–3684; YONEDA, R.; HARUSAWA, S.; KURIHARA, T. J. Org. Chem. 1991, 56, 1827–1832). A solution of 1-methyl-1H-indole-7-carboxaldehyde (137 mmol, crude material prepared as described above), LiCN 1.5 THF complex (1.94 g, 13.7 mmol), and diethylcyanophosphonate (27.1 mL, 179 mmol) in THF (400 mL) was stirred at room temperature overnight. Tert-butanol (13.1 mL, 137.7 mmol) was introduced and the mixture was transferred via cannula into a 0.1 M solution of SmI2 in THF (3.6 L, 360 mmol) and the mixture stirred for 30 minutes. The mixture was concentrated to dryness, the residue was taken up in EtOAc (2 L), and the solution was washed with 1N HCl (3×500 mL), saturated aq NaHCO3, and brine. The solution was dried (MgSO4), passed through a pad of silica gel, and concentrated to give the title compound in sufficient purity for use in the next step. Flash chromatography (90% hexane/EtOAc) can be used to afford the title compound pure, as an off-white crystalline solid. 1H (400 MHz, DMSO-d6) 7.51 (d, J=7.5 Hz, 1H), 7.28 (d, J=3 Hz, 1H), 7.09 (d, J=7.5 Hz, 1H), 6.99 (dd, J=7.5, 7.5 Hz, 1H), 6.43 (d, J=3 Hz, 1H), 4.58 (s, 2H), 4.07 (s, 3H). 13C NMR (75.5 MHz, DMSO-d6) 133.56, 131.89, 130.06, 122.38, 120.74, 119.53, 119.16, 114.47, 100.59, 35.86, 20.43. IR (CHCl3, cm−1) 2252. MS (electrospray, m/z) 171 (M++1). Anal. Calcd for C11H10N2: C, 77.62; H, 5.92; N, 16.46. Found: C, 77.62; H, 5.96; N, 16.38.

1. concentrationThe mixture was concentrated to dryness
2. washthe solution was washed with 1N HCl (3×500 mL), saturated aq NaHCO3, and brine
3. dry with materialThe solution was dried (MgSO4)
4. concentrationconcentrated

ORD record

ord-b161af80a8be425984c3bf8b3da29661

Source dataset

uspto-grants-2006_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07109229B2