氯苄羟基保护.pdfVIP

Organic Syntheses, Coll. Vol. 7, p.34 (1990); Vol. 63, p.214 (1985). INDOLES FROM 2-METHYLNITROBENZENES BY CONDENSATION WITH FORMAMIDE ACETALS FOLLOWED BY REDUCTION: 4-BENZYLOXYINDOLE [1H-Indole, 4-(phenylmethoxy)-] Submitted by Andrew D. Batcho1 2 and Willy Leimgruber . Checked by David J. Wustrow and Andrew S. Kende. 1. Procedure A. 6-Benzyloxy-2-nitrotoluene. A stirred mixture of 124.7 g (0.81 mol) of 2-methyl-3-nitrophenol (Note 1), 113.2 g (0.90 mol) of benzyl chloride, 112.2 g (0.81 mol) of anhydrous potassium carbonate, and 800 mL of dimethylformamide (DMF) is heated at 90°C for 3 hr. Most of the DMF is removed on a rotary evaporator (20 mm) and the oily residue is poured into 400 mL of 1 N sodium hydroxide and extracted with ether (3 × 800 mL). The combined extracts are dried (Na SO ), filtered, and evaporated 2 4 to give 203.5 g of yellowish solid. Recrystallization from 1 L of methanol cooled to 0°C affords 177.6 (90%) of 6-benzyloxy-2-nitrotoluene as pale-yellow crystals, mp 61–63°C3 (Note 2). B. (E)-6-Benzyloxy-2-nitro-β-pyrrolidinostyrene. To a solution of 175.4 g (0.72 mol) of 6- benzyloxy-2-nitrotoluene in 400 mL of DMF are added 102.5 g (0.84 mol) of N,N-dimethylformamide dimethyl acetal (Note 3) and 59.8 g (0.84 mol) of pyrrolidine. The solution is heated at reflux (110°C) for 3 hr (Note 4) under nitrogen and allowed to cool to room temperature. The volatile components are removed on a rotary evaporator, and the red residue (Note 5) is dissolved in 200 mL of methylene chloride and 1.60 L of methanol. The solution is concentrated to a volume of about 1.40 L on the steam