Reaction SMILES: Cl.NO.ClC1C=CC(CN2CCC(C(=O)C=C(O)C3C=CC(Cl)=CC=3)CC2)=CC=1.C(N(C(C)C)C(C)C)C.[Cl:39][C:40]1[CH:65]=[CH:64][C:43]([CH2:44][N:45]2[CH2:50][CH2:49][CH:48]([CH:51]3[O:55][NH:54][C:53]([C:57]4[CH:62]=[CH:61][C:60]([Cl:63])=[CH:59][CH:58]=4)(O)[CH2:52]3)[CH2:47][CH2:46]2)=[CH:42][CH:41]=1.ClC1C=CC(CN2CCC(C3(O)CC(C4C=CC(Cl)=CC=4)ON3)CC2)=CC=1.CS(Cl)(=O)=O>CO.CN(C=O)C.ClCCl.C(OCC)(=O)C.C(N(CC)CC)C.O>[Cl:39][C:40]1[CH:41]=[CH:42][C:43]([CH2:44][N:45]2[CH2:46][CH2:47][CH:48]([C:51]3[O:55][N:54]=[C:53]([C:57]4[CH:58]=[CH:59][C:60]([Cl:63])=[CH:61][CH:62]=4)[CH:52]=3)[CH2:49][CH2:50]2)=[CH:64][CH:65]=1
Reactant: OC1(c2ccc(Cl)cc2)CC(C2CCN(Cc3ccc(Cl)cc3)CC2)ON1
Agent: CS(=O)(=O)Cl
Agent: Cl
Agent: NO
Solvent: O
Solvent: ClCCl
Solvent: CO
Product: Clc1ccc(CN2CCC(c3cc(-c4ccc(Cl)cc4)no3)CC2)cc1
Temperature: 50 °C
Reaction time: 4 h

Procedure:
Hydroxylamine hydrochloride (139 mg) was added to 1-(4-chlorobenzyl)-4-(3-hydroxy-1-oxo-3-(4-chlorophenyl)prop-2-en-1-yl)piperidine obtained from Example 1 (399 mg) and ethyldiisopropylamine (0.35 ml) in methanol (5 ml) and DMF (2 ml). After stirring for 16 h hydroxylamine hydrochloride (139 mg) and ethyldiisopropylamine (0.35 ml) were added and the mixture stirred at 50° C. for 4 h. Water (50 ml) was added, the mixture extracted with ethyl acetate (3×25 ml) and the combined organic layers washed with water and brine, dried (MgSO4), evaporated in vacuo, and purified by flash chromatography, eluting with dichloromethane:methanol:triethylamine (96:4:1 v/v) to give a mixture of 5-(1-(4-chlorobenzyl)-4-piperidinyl)-3-(4-chlorophenyl)-3-hydroxy-3,4-dihydroisoxazole and 3-(1-(4-chlorobenzyl)-4-piperidinyl)-5-(4-chlorophenyl)-3-hydroxy-3,4-dihydroisoxazole (287 mg). 209 mg of this oil was dissolved in dichloromethane (5 ml), cooled to 0° C., and triethylamine (161 mg) and methanesulphonyl chloride (81 mg) added. After 1 h ethyl acetate (25mg) was added, and the mixture washed with water and brine, dried (MgSO4), and evaporated in vacuo, and purified by preparative thin layer chromatography, eluting with dichloromethane:methanol:triethylamine (97:3:1 v/v) to give 5-(1-(4-chlorobenzyl)-4-piperidinyl)-3-(4-chlorophenyl)isoxazole (107 mg); oxalate salt: amorphous white solid, m.p.227°-230° C. (from ethanol) (Found: C, 58.91; H, 4.95; N, 6.15%. C21H20N2OCl2. (0.8C2H2O4) requires C, 59.09; H, 4.74; N, 6.10%); δH (360 MHz, d6 -DMSO) 1.7-1.8 (2H, m, CHCHAHB), 2.08 (2H, d, J=11, CHCHAHB), 2.3-2.4 (2H, m, NCHAHB), 3.0-3.1 (3H, m, NCHAHB and CH2CH), 3.82 (2H, s, ArCH2), 6.92 (1H, s, CHCO), 7.4-7.5 (4H, m, ArHCH2), 7.59 (2H, d, J=8, ArH), 7.88 (2H, d, J=8, ArH); m/z (CI+, NH3) 387 (M+ +H); and 3-(1-(4-chlorobenzyl)-4-piperidinyl)-5-(4-chlorophenyl)isoxazole (51 mg); oxalate salt: white plates, m.p. 240°-242° C. (from ethanol) (Found: C, 57.85; N, 4.74; H, 5.92. C21H20N2OCl2.C2H2O4 requires C, 57.87; H, 4.64; N 5.87%); δH (d6 -DMSO) 1.8-1.9 (2H, m, CHAHBCH), 2.05 (2H, d, J=11, CHAHBCH), 2.6-2.7 (2H, m, NCHAHB), 2.9-3.0 (1H, m, CH2CH), 3.1-3.2 (2H, m, NCHAHB), 3.97 (2H, s, ArCH2), 7.07 (1H, s, CHCO), 7.4-7.5 (4H, m ArHCH2), 7.61 (2H, d, J=8, ArH), 7.85 (2H, d, J=8, ArH); m/z (CI+, NH3) 387 (M+ +H). The isoxazole regiochemistry was proved by X-ray.