3-(5-chloro-2-methylphenyl)propanal

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-chloro-2-(3-oxopropyl)toluene in MeOH was added excess NaBH4 at room temperature and the mixture was diluted with water, treated with 1N HCl, and extracted with AcOEt. The extracts was dried and concentrated to give quantitatively the title compound: 1H NMR (CDCl3) δ7.14 (bd, 1H, J=9 Hz), 7.06 (d, 1H, J=9 Hz), 7.05 (bs, 1H), 3.66~3.77 (m, 2H), 2.68 (t, 2H, J=7.2 Hz), 2.30 (s, 3H), 1.83 (5et, 2H, J=7.2 Hz), 1.35~1.44 (br, 1H). extracted with AcOEt The extracts was dried concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 2-amino-4-chlorotoluene (1.41 g, 10 mmol) in 24% aq. HCl (5 mL) Was added dropwise NaNO2 (710 mg, 1.03 mmol) in H2O (3 mL) over 30 min at 0° C. The resulting solution was added dropwise to a solution of acrolein (1 mL, 15 mmol) in a mixture of DMF (15 mL) and 20% aq. TiCl3 (20 mL, 26 mmol). After the addition was completed, the mixture was stirred for 30 min at room temperature and extracted with diethyl ether. The extracts was dried over MgSO4 and concentrated. The residue was purified by silica gel column chromatography with 5:1 hexane/AcOEt to give 1.11 g of the title compound (60%): 1H NMR (CDCl3) δ9.83 (s, 1H), 7.06~7.12 (m, 3H), 2.90 (t, 2H, J=7.2 Hz), 2.74 (t, 2H, J=7.2 Hz), 2.27 (s, 3H). After the addition extracted with diethyl ether The extracts was dried over MgSO4 concentrated The residue was purified by silica gel column chromatography with 5:1 hexane/AcOEt