3-bromo-4-methoxybenzaldehyde

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of sodium ethylate in ethanol (prepared from sodium (1.92 g; 83.70 mmol) and EtOH (40 mL)) was added dropwise to a cold (−10° C.) solution of 3-bromo-p-anisaldehyde (4 g; 18.60 mmol) and ethyl azidoacetate (ABCR, 27.80 ml; 46.50 mmol) in EtOH (60 mL). After the end of the addition, the reaction mixture was warmed up to 0° C. and stirred at RT for 5 hours. The heterogenous mixture was poured onto ice and stirred for 30 minutes. The solid was collected by filtration and dried under high vacuum. The solid was taken up in xylenes (60 mL) and heated to reflux for 3 hours. The solvent was evaporated and the residue was purified by silica column chromatography (c-Hexane/ethyl acetate, 80/20) to give the title compound as a pale yellow solid. 1H NMR (DMSO-d6) δ 11.87 (s, 1H), 7.89 (s, 1H), 7.05 (s, 1H), 6.98 (s, 1H), 4.31 (q, J=7 Hz, 2H), 3.85 (s, 3H), 1.32 (t, J=7 Hz, 3H). HPLC (Method A), Rt 4.28 min (Purity: 98.1%). LC/MS (Method B): 297.2 (M+H)+. After the end of the addition The heterogenous mixture was poured onto ice stirred for 30 minutes The solid was collected by filtration dried under high vacuum heated to reflux for 3 hours The solvent was evaporated the residue was purified by silica column chromatography (c-Hexane/ethyl acetate, 80/20)

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

Procedure: Addition of 3-bromo-4-methoxybenzaldehyde to acetonitrile gave 3-(3-bromo-4-methoxyphenyl)-3-hydroxypropanenitrile as a pale orange oil. Yield (10.32 g, 96%): 1H NMR (400 MHz, DMSO-d6) δ 7.58 (d, J=2.0 Hz, 1H), 7.35 (dd, J=8.8, 2.0 Hz, 1H), 7.07 (d, J=8.8 Hz, 1H), 5.93 (d, J=4.4 Hz, 1H), 4.85-4.81 (m, 1H). 3.81 (s, 3H), 2.86 (ABd, J=16.4, 4.8 Hz, 1H), 2.79 (ABd, J=16.8, 6.8 Hz, 1H).

Conditions: temp:0.00; pressure:0.00; stir: