2-butyl-1-benzofuran-3-carbaldehyde

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: At ambient temperature, to a stirred solution containing 2-n-butylbenzofuran-3-carboxaldehyde (0.888 g, 4.77 mmol) and 4-aminophenol hydrochloride in MeOH (7 mL) was added sodium cyanoborohydride (0.330 g, 5.25 mmol). After 24 h, the reaction was carefully quenched with 3N HCl, diluted with H2O and extracted with CH2Cl2. The organic extracts were washed with sat. aq. NaHCO3, dried and concentrated. Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient gave the title compound as a pale yellow solid. 1H NMR (CDCl3) δ0.93 (t, 3H), 1.38 (sextet, 2H), 1.70 (quintet, 2H), 2.79 (t, 2H), 4.27 (s, 1H), 4.35 (br. s, 1H), 6.62 (d, 2H), 6.75 (d, 2H), 7.18-7.26 (m, 3H), 7.41 (d, 1H), 7.54 (d, 1H). the reaction was carefully quenched with 3N HCl diluted with H2O extracted with CH2Cl2 The organic extracts were washed with sat. aq. NaHCO3 dried concentrated Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient

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

Procedure: At ambient temperature, to a stirred solution containing 2-n-butylbenzofuran-3-carboxaldehyde (0.888 g, 4.77 mmol) and 4-aminophenol hydrochloride in MeOH (7 mL) was added sodium cyanoborohydride (0.330 g, 5.25 mmol). After 24 h, the reaction was carefully quenched with 3N HCl, diluted with H2O and extracted with CH2Cl2. The organic extracts were washed with sat. aq. NaHCO3, dried and concentrated. Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient gave the title compound as a pale yellow solid. 1H NMR (CDCl3) δ0.93 (t, 3H), 1.38 (sextet, 2H), 1.70 (quintet, 2H), 2.79 (t, 2H), 4.27 (s, 1H), 4.35 (br. s, 1H), 6.62 (d, 2H), 6.75 (d, 2H), 7.18-7.26 (m, 3H), 7.41 (d, 1H), 7.54 (d, 1H). the reaction was carefully quenched with 3N HCl diluted with H2O extracted with CH2Cl2 The organic extracts were washed with sat. aq. NaHCO3 dried concentrated Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient

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

Procedure: To a mixture of 2-butyl-1-benzofuran-3-carbaldehyde (25 g, 0.124 mol) and sodium acetate (12.2 g, 0.124 mol) in methanol (100 mL) was added hydroxylamine hydrochloride (10.3 g, 0.149 mol) in water (25 mL) at 0° C. The mixture was stirred at rt for 2 h. Water (300 mL) was added to the reaction mixture and the product was extracted with EtOAc. The organic layer was dried and concentrated under vacuum to give crude 2-butyl-1-benzofuran-3-carbaldehyde oxime (25 g, 93%) as a light brown liquid. the product was extracted with EtOAc The organic layer was dried concentrated under vacuum

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

Procedure: To a solution of DMF (59 g, 0.805 mol) in anhydrous DCM (300 mL) was added slowly at 0° C. under N2 atmosphere phosphorous oxy-chloride (123 g, 0.84 mol). The mixture was stirred at rt for 2 h. To this was added slowly 2-butyl-1-benzofuran (35 g, 0.21 mol) in anhydrous DCM (100 mL). The reaction mixture was slowly heated to 60° C. for 72 h, cooled to rt and poured into ice and extracted with EtOAc. The organic layer was washed with water, brine and dried over MgSO4. The solvent was removed under vacuum and the crude product purified by column chromatography over silica gel (PetEther/EtOAc) to give 2-butyl-1-benzofuran-3-carbaldehyde (30 g, 74%) as a light brown liquid. The reaction mixture was slowly heated to 60° C. for 72 h cooled to rt poured into ice extracted with EtOAc The organic layer was washed with water, brine dried over MgSO4 The solvent was removed under vacuum the crude product purified by column chromatography over silica gel (PetEther/EtOAc)

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

Procedure: To a solution of DMF (59 g, 0.805 mol) in anhydrous DCM (300 mL) was added slowly at 0° C. under N2 atmosphere phosphorous oxy-chloride (123 g, 0.84 mol). The mixture was stirred at rt for 2 h. To this was added slowly 2-butyl-1-benzofuran (35 g, 0.21 mol) in anhydrous DCM (100 mL). The reaction mixture was slowly heated to 60° C. for 72 h, cooled to rt and poured into ice and extracted with EtOAc. The organic layer was washed with water, brine and dried over MgSO4. The solvent was removed under vacuum and the crude product purified by column chromatography over silica gel (PetEther/EtOAc) to give 2-butyl-1-benzofuran-3-carbaldehyde (30 g, 74%) as a light brown liquid. The reaction mixture was slowly heated to 60° C. for 72 h cooled to rt poured into ice extracted with EtOAc The organic layer was washed with water, brine dried over MgSO4 The solvent was removed under vacuum the crude product purified by column chromatography over silica gel (PetEther/EtOAc)

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

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

Procedure: At ambient temperature, to a stirred solution containing 2-n-butylbenzofuran-3-carboxaldehyde (0.888 g, 4.77 mmol) and 4-aminophenol hydrochloride in MeOH (7 mL) was added sodium cyanoborohydride (0.330 g, 5.25 mmol). After 24 h, the reaction was carefully quenched with 3N HCl, diluted with H2O and extracted with CH2Cl2. The organic extracts were washed with sat. aq. NaHCO3, dried and concentrated. Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient gave the title compound as a pale yellow solid. 1H NMR (CDCl3) δ 0.93 (t, 3 H), 1.38 (sextet, 2 H), 1.70 (quintet, 2 H), 2.79 (t, 2 H), 4.27 (s, 1 H), 4.35 (br. s, 1 H), 6.62 (d, 2 H), 6.75 (d, 2 H), 7.18-7.26 (m, 3 H), 7.41 (d, 1 H), 7.54 (d, 1 H). the reaction was carefully quenched with 3N HCl diluted with H2O extracted with CH2Cl2 The organic extracts were washed with sat. aq. NaHCO3 dried concentrated Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient

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

Procedure: At ambient temperature, to a stirred solution containing 2-n-butylbenzofuran-3-carboxaldehyde (0.888 g, 4.77 mmol) and 4-aminophenol hydrochloride in MeOH (7 mL) was added sodium cyanoborohydride (0.330 g, 5.25 mmol). After 24 h, the reaction was carefully quenched with 3N HCl, diluted with H2O and extracted with CH2Cl2. The organic extracts were washed with sat. aq. NaHCO3, dried and concentrated. Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient gave the title compound as a pale yellow solid. 1H NMR (CDCl3) δ 0.93 (t, 3H), 1.38 (sextet, 2H), 1.70 (quintet, 2H), 2.79 (t, 2H), 4.27 (s, 1H), 4.35 (br. s, 1H), 6.62 (d, 2H), 6.75 (d, 2H), 7.18-7.26 (m, 3H), 7.41 (d, 1H), 7.54 (d, 1H). the reaction was carefully quenched with 3N HCl diluted with H2O extracted with CH2Cl2 The organic extracts were washed with sat. aq. NaHCO3 dried concentrated Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient

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

Procedure: At ambient temperature, to a stirred solution containing 2-n-butylbenzofuran-3-carboxaldehyde (0.888 g, 4.77 mmol) and 4-aminophenol hydrochloride in MeOH (7 mL) was added sodium cyanoborohydride (0.330 g, 5.25 mmol). After 24 h, the reaction was carefully quenched with 3N HCl, diluted with H2O and extracted with CH2Cl2. The organic extracts were washed with sat. aq. NaHCO3, dried and concentrated. Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient gave the title compound as a pale yellow solid. 1H NMR (CDCl3) δ0.93 (t, 3H), 1.38 (sextet, 2H), 1.70 (quintet, 2H), 2.79 (t, 2H), 4.27 (s, 1H), 4.35 (br. s, 1H), 6.62 (d, 2H), 6.75 (d, 2H), 7.18-7.26 (m, 3H), 7.41 (d, 1H), 7.54 (d, 1H). the reaction was carefully quenched with 3N HCl diluted with H2O extracted with CH2Cl2 The organic extracts were washed with sat. aq. NaHCO3 dried concentrated Purification on silica gel eluting with a 20 & 40% EtOAc/pet. ether step gradient