Dimethyl Sulfoxide → Phenylmethyl 2-formyl-2,3-dihydro-1H-indole-1-carboxylate

Participants

Reaction Steps

Dimethyl sulfoxide (2.75 ml) is added to a solution of oxalyl chloride (1.7 ml) in methylene chloride (45 ml) at -78° under nitrogen via cannula over six minutes. After 20 minutes, (±) 1-benzyloxycarbonyl-2-hydroxymethylindoline (IV, EXAMPLE 4, 5.003 g) in methylene chloride (20 ml) is added via cannula over 12 minutes. The mixture is stirred for 30 minutes, then triethyl amine (7.40 ml) is added. The mixture is stirred at -78° for an additional 20 minutes then stirred at 20°-25° for one hour, then poured into water (50 ml) and the layers are separated. The aqueous layer is extracted with methylene chloride (5×20 ml). The combined organic layers are washed sequentially with saline, hydrochloric acid (3N, 100 ml), water (100 ml), aqueous sodium carbonate (5%, 100 ml) and again with water (100 ml). The organic layer is then dried over magnesium sulfate and concentrated under reduced pressure to give an oil. The oil is passed over a silica column (27.5 cm×4.0 cm, 40-63 mm) and is eluted with ethyl acetate/hexane (1/5.6 300 ml, 1/42 l), collecting 29 ml fractions. The appropriate fractions are pooled and concentrated to give the title compound, NMR (CDCl3, 300 MHz) 9.62, 7.93, 7.34, 7.20, 7.11, 6.97, 5.23, 4.82, 3.36 and 3.13 δ; CMR (CDCl3, 75.47 MHz) 29.74, 65.76, 67.57, 115.05, 123.34, 124.64, 128.08, 128.20, 128.40, 128.61, 135.57, 141.7, 151.9 and 198.73 δ; IR (CHCl3) 2940, 1700, 1600, 1480, 1400, 1320, 1270-1190 and 1030 cm-1 ; MS (m/e) 281, 252, 208, 117, 91 and 65 , exact mass calcd for C17H15NO3 (281.1052), found 281.1066; TLC (ethyl acetate/hexane, 1/3) Rf =0.28.

Provenance & Evidence