Ammonia → (R)-3-(2-(1-methylpyrrolidin-2-yl)ethyl)-1H-indol-5-amine

Participants

Reaction Steps

To an argon purged round bottom flask fitted with a magnetic stirbar and containing a yellow solution of 145 (94 g, 0.292 mmol) in anhydrous 2-propanol (6 mL) and water (2 mL) was added solid hydroxylamine hydrochloride (406 mg, 5.84 mmol) in one portion. Triethylamine (407 mL, 2.92 mmol) was added via syringe and the flask was fitted with a condenser. The vessel was placed in an oil bath and heated to reflux. The reaction was stirred at reflux under argon for 6 hours. TLC (10% 2M NH3 in MeOH, 90% CH2Cl2) revealed the reaction was complete, and so the reaction was cooled to room temperature. Sodium hydroxide pellets (120 mg, 3.0 mmol) were added slowly. The reaction was stirred vigorously overnight. The reaction was filtered through celite, followed by washing of the celite with 2-propanol (40 mL) and absorption of the filtrate onto silica gel. The product was purified by column chromatography (5-10% 2M NH3 in MeOH, 90% CH2Cl2) using a silica gel plug approximately 15 mm in diameter by 30 mm in height to afford an orange solid. This product was partitioned between brine (5 mL) and ethyl acetate (10 mL). The organic was dried with anhydrous sodium sulfate before being decanted. Concentration afforded an orange oil, compound 146. Yield: 48 mg of orange oil (68%) 1H NMR (DMSO-d6) δ 10.19 (s, 1H), 7.02-6.99 (d, J=5.4 Hz, 1H), 6.90-6.89 (d, J=2.1 Hz, 1H), 6.64-6.63 (d, J=1.5 Hz, 1H), 6.47-6.43 (dd, J=1.8, 8.7 Hz, 1H), 4.42 (bs, 1H), 2.97-2.90 (m, 1H), 2.59 (m, 2H), 2.20 (s, 3H), 2.05-1.97 (m, 4H), 1.69-1.40 (m, 4H).

Provenance & Evidence