Reaction SMILES: [CH3:1][O:2][CH:3]=[C:4]1[O:8][NH:7][C:6]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)=[C:5]1[C:16](OC)=[O:17].[H-].C([Al+]CC(C)C)C(C)C>C1(C)C=CC=CC=1>[OH:17][CH:16]=[C:5]1[C:4](=[CH:3][O:2][CH3:1])[O:8][N:7]=[C:6]1[C:9]1[CH:10]=[CH:11][C:12]([F:15])=[CH:13][CH:14]=1
Reactant: COC=C1ONC(c2ccc(F)cc2)=C1C(=O)OC
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: Cc1ccccc1
Product: COC=c1onc(-c2ccc(F)cc2)c1=CO
Temperature: -78 °C
Reaction time: 1.5 h
Yield: 52.7 %

Procedure:
A suspension of methyl 5-methoxymethylene-3-[4-fluorophenyl]isoxazole 4-carboxylate (30 g, 0.113 mol) in 100 ml anhydrous toluene was cooled to −78° C. under nitrogen. Diisobutyl aluminium hydride (250 ml of 1.0 M solution in toluene) was added slowly and the reaction allowed to stir at −78° C. for 1.5 h. The reaction was quenched with methanol then partitioned between CH2Cl2—H2O. The organic extracts were washed with brine, dried (MgSO4), and concentrated to give the title compound as a yellow oil (14 g). 1H NMR (400 MHz, CDCl3) δ 7.79–7.75 (2H, m), 7.26–7.15 (2H, m), 4.67 (2H, s), 4.61–4.60 (2H, m), 3.50 (3H, s). c) 5-Methoxymethylene-3-[4-fluorophenyl]isoxazole 4-carboxaldehyde A suspension of Dess-Martin periodinane (8.26 g) in 50 ml CH2Cl2 was stirred at room temperature with 3 ml pyridine to give a turbid reaction. A solution of 4-hydroxymethylene-5-methoxymethylene-3-[4-fluorophenyl]isoxazole (4.2 g, 17.7 mmol) in 50 ml CH2Cl2 was added dropwise over 5 minutes and the reaction stirred for 30 minutes. The reaction was quenched with 1:1 NaHCO3—NaHSO3 and stirred for 1 h, extracted into CH2Cl2, washed with brine, dried (MgSO4), and concentrated. Purification by chromatography using 20% EtOAc-isohexanes as eluent gave the title compound as a colourless solid (3.7 g, 89%). 1H NMR (400 MHz, CDCl3) δ 10.07 (1H, s), 7.77–7.73 (2H, m), 7.26–7.14 (2H, m), 4.90 (2H, s), 3.53 (3H, s). d) 8-Bromo-3-(5-methoxymethylenyl-3-[4-fluorophenyl]isoxazol-4-yl)-5H-[1,2,4]triazolo[3,4-a]isoindole 5-Methoxymethylene-3-[4-fluorophenyl]isoxazole-4-carboxaldehyde (0.66 g) and (6-bromo-3H-isoindol-1-yl)hydrazine (0.64 g, 2.83 mmol) were reacted in a similar manner to that described in Example 4 to give the title compound (0.6 g). m/z (ES+) 441/443 (M+H)+1H NMR (400 MHz, d6-DMSO) δ 8.141–8.145 (1H, m), 7.703–7.708 (1H, m), 7.59–7.64 (3H, m), 7.27 (2H, m), 4.73–4.74(4H, m), 3.32 (3H, s). e) 8-Bromo-3-(5-hydroxymethylenyl-3-[4-fluorophenyl]isoxazol-4-yl)-5H-[1,2,4]triazolo[3,4-a]isoindole A solution of 8-bromo-3-(5-methoxymethylenyl-3-[4-fluorophenyl]isoxazol-4-yl)-5H-[1,2,4]triazolo[3,4-a]isoindole (170 mg, 3.85 mmol) in 5 ml CH2Cl2 was cooled to −78° C. under a nitrogen atmosphere. Boron tribromide (250 μl) was added and the reaction allowed to attain room temperature. The reaction was re-cooled to 0° C. and quenched by addition of Et2O followed by H2O. The residue was concentrated and purified using dry flash column chromatography and CH2Cl2 then 3% MeOH—CH2Cl2 as eluent. The title compound was obtained after crystallisation from iPrOH (135 mg, 82%). 1H NMR (400 MHz, d6-DMSO) δ 8.13 (1H, s), 7.70–7.72 (1H, m), 7.57–7.64 (3H, m), 7.27–7.32 (2H, m), 5.82 (1H, t, J=8.8 Hz), 4.80 (2H, s), 4.73–4.75 (2H, d, J=8.8 Hz). m/z (ES+) 427/429 (M+H)+.