A slurry of calcium hydroxide 5.18g (70mmol) in a neat mixture of 2-chloro-3-nitrotoluene 6.580g (38.34mmol) and 4,4-(ethylenedioxo)-piperidine 13mL (100mmol) was stirred without solvent in a closed pressure glass flask at 180C for 10 hours (overnight). The flask was cooled to ambient temperature, the sludge was diluted with ether 100mL and briefly sonicated to break the lumpy solids. The inorganics were removed by filtration, washed with additional ether (150mL) and discarded. The combined filtrates were washed with 1M aqueous citric acid (2x200mL), then with water (200mL) and saturated NaHCO3 (200mL). The aqueous phases were re-extracted with ether (200mL). The combined extracts were dried (MgSO4) and evaporated. The obtained oil was dissolved in cyclohexane 50mL and the solution was left to RIP at RT for 1 day. Decanting the supernatants and washing the deposited chunky orange crystals with pentane and in vacuo drying provided 7.762g of a pure product. The combined supernatants and pentane washings were passed through a 2x2inch pad of silica, the silica was then washed with dichloromethane 150mL and the combined filtrates were evaporated. The evaporation residue was re-crystallised from cyclohexane 10mL to provide the second crop, 1.312g of pure product as a bright-yellow gem quality rhombs.
The combined yield was 9.074g (85%Y).
This nitro-compound, 7.760g (27.88mmol) was then hydrogenated in the presence of 5% platinum on carbon, 0.51g [Aldrich 205931] in ethyl acetate (150mL) at RT under hydrogen balloon for 3h 30min. The mixture was filtered through a pad of Celite to remove the catalyst (the pad was washed with additional EtOAc) and the filtrates were evaporated. The crystalline residue was dried on highvac. Y=6.860g (99%) of a white crystalline solid.
1H(d6-DMSO, 400MHz): 6.704(t, 7.6Hz, 1H), 6.496(dd, 7.8Hz, 1.2Hz, 1H), 6.253(d, 7.2Hz, 1H), 4.857(br s, 2H), 3.905(m, 4H), 3.204(td, t:11.5Hz, d:2.3Hz, 2H), 2.786(br m, 2H), 2.195(s, 3H), 1.812(td, t:11.7Hz, d:4.6Hz, 2H), 1.655(br d, 11.1Hz, 2H); 13C(d-6DMSO, 100MHz): 145.63, 135.66, 134.76, 125.45, 118.91, 112.15, 106.61, 63.64, 63.52, 47.24(2C), 35.97(2C), 19.41