4-formyl-3-hydroxybenzonitrile

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:; See reaction.notes.procedure_details.

Procedure: 33.1 g of 4-formyl-3-hydroxybenzonitrile (Liebigs Ann. Chem. (1982) 1836) were O-benzylated with 1 eq. each of benzyl bromide and K2CO3 and, after workup, reduced with NaBH4 in 100 ml of MeOH/THF 2:3 at -10° C. to 0° C. to give the alcohol. 22.4 g were obtained. The product could be crystallized from DCM/petroleum ether. 1H-NMR (CDCl3, δ in ppm): 7.48 (1H), 7.40-7.3 (5H), 7.20 (1H), 7.08 (1H), 5.05 (s, 2H), 4.75 (s, 2H), 2.85 (1H, OH)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-cyano-2-fluorobenzaldehyde (11.73 g, 78.7 mmol) and potassium carbonate (14.12 g, 102.3 mmol) was dissolved in dry dimethylformamide (35 ml). To this was added water (6.63 ml, 368.5 mmol). The resulting solution was heated to 90° C. with stirring. A further equivalent of water (1.42 ml) was added after 2 hours, then a further two equivalents of water (2.84 ml) 1 hour later. The resulting solution was left overnight. After 24 hours a further 2 equivalents of water (2.84 ml) was added, then heated for a further 2 hours at 90° C. The cooled solution was diluted with water to form a murky yellow solution. The solid precipitate was filtered. The remaining yellow filtrate was acidified with concentrated hydrochloric acid to produce a yellow solid. This was filtered, then dried at 40° C. overnight to give 4-cyano-2-hydroxybenzaldehyde as a yellow solid. heated for a further 2 hours at 90° C to form a murky yellow solution The solid precipitate was filtered to produce a yellow solid This was filtered dried at 40° C. overnight

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

Procedure: 33.1 g of 4-formyl-3-hydroxybenzonitrile (Liebigs Ann. Chem. (1982) 1836) were O-benzylated with 1 eq. each of benzyl bromide and K2CO3 and, after workup, reduced with NaBH4 in 100 ml of MeOH/THF 2:3 at -10° C. to 0° C. to give the alcohol. 22.4 g were obtained. The product could be crystallized from DCM/petroleum ether. 1H-NMR (CDCl3, δ in ppm): 7.48 (1H), 7.40-7.3 (5H), 7.20 (1H), 7.08 (1H), 5.05 (s, 2H), 4.75 (s, 2H), 2.85 (1H, OH)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-cyano-2-fluorobenzaldehyde (11.73 g, 78.7 mmol) and potassium carbonate (14.12 g, 102.3 mmol) was dissolved in dry dimethylformamide (35 ml). To this was added water (6.63 ml, 368.5 mmol). The resulting solution was heated to 90° C. with stirring. A further equivalent of water (1.42 ml) was added after 2 hours, then a further two equivalents of water (2.84 ml) 1 hour later. The resulting solution was left overnight. After 24 hours a further 2 equivalents of water (2.84 ml) was added, then heated for a further 2 hours at 90° C. The cooled solution was diluted with water to form a murky yellow solution. The solid precipitate was filtered. The remaining yellow filtrate was acidified with concentrated hydrochloric acid to produce a yellow solid. This was filtered, then dried at 40° C. overnight to give 4-cyano-2-hydroxybenzaldehyde as a yellow solid. heated for a further 2 hours at 90° C to form a murky yellow solution The solid precipitate was filtered to produce a yellow solid This was filtered dried at 40° C. overnight

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

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

Procedure: 33.1 g of 4-formyl-3-hydroxybenzonitrile (Liebigs Ann. Chem. (1982) 1836) were O-benzylated with 1 eq. each of benzyl bromide and K2CO3 and, after workup, reduced with NaBH4 in 100 ml of MeOH/THF 2:3 at −10° C. to 0° C. to give the alcohol. 22.4 g were obtained. The product could be crystallized from DCM/petroleum ether.

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

Procedure: 2.4 ml (14.27 mmol) of trifluoromethanesulfonic anhydride are added dropwise to a solution of 2 g (13.59 mmol) of 4-formyl-3-hydroxybenzonitrile and 2.5 ml (14.27 mmol) of N,N-diisopropylethylamine in 37 ml of anhydrous dichloromethane at 0° C. under an argon atmosphere. The reaction mixture is stirred at RT for 1 h, then diluted with 70 ml of dichloromethane and washed successively with 1 M hydrochloric acid, saturated sodium bicarbonate solution and saturated sodium chloride solution. The organic solution is dried over magnesium sulfate and concentrated. The residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 7:1). 2.36 g (62% of theory) of the title compound are obtained as a white solid. washed successively with 1 M hydrochloric acid, saturated sodium bicarbonate solution and saturated sodium chloride solution The organic solution is dried over magnesium sulfate concentrated The residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 7:1)

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

Procedure: 100 ml of a boron tribromide solution in dichloromethane (1 M, 100 mmol) are added dropwise to a solution of 8 g (49.64 mmol) of 4-formyl-3-methoxybenzonitrile in 80 ml of anhydrous dichloromethane at −78° C. under an argon atmosphere. The reaction mixture is stirred at RT until the precursor has completely reacted (about 5 days). The reaction solution is then neutralized at 0° C. with saturated sodium bicarbonate solution. The phases are separated and the organic phase is washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated. The residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 3:1). 4.5 g (61% of theory) of the title compound are obtained as a yellow solid. has completely reacted (about 5 days) The phases are separated the organic phase is washed with saturated sodium chloride solution dried over magnesium sulfate concentrated The residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 3:1)

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

Procedure: 2.4 ml (14.27 mmol) of trifluoromethanesulfonic anhydride are added dropwise to a solution of 2 g (13.59 mmol) of 4-formyl-3-hydroxybenzonitrile and 2.5 ml (14.27 mmol) of N,N-diisopropyl-ethylamine in 37 ml of anhydrous dichloromethane at 0° C. under an argon atmosphere. The reaction mixture is stirred at RT for 1 h, then diluted with 70 ml of dichloromethane and washed successively with 1 M hydrochloric acid, saturated sodium bicarbonate solution and saturated sodium chloride solution. The organic solution is dried over magnesium sulfate and concentrated. The residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 7:1). 2.36 g (62% of theory) of the title compound are obtained as a white solid. washed successively with 1 M hydrochloric acid, saturated sodium bicarbonate solution and saturated sodium chloride solution The organic solution is dried over magnesium sulfate concentrated The residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 7:1)