(4-chloro-3-methoxyphenyl)methanol

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

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

Procedure: A suspension of pyridinium chlorochromate (1.37 g, 6.34 mmol) in dichloromethane (35 mL) was treated with Celite (2.0 g) and stirred at rt. A solution of (4-chloro-3-methoxyphenyl)methanol (730 mg, 4.23 mmol) in dichloromethane (5 mL) was added in one portion, and the resulting mixture was stirred at rt for 3 h. After this time, the mixture was diluted with diethyl ether, and stirred vigorously. The mixture was then filtered through a pad of silica gel and the collected solids were rinsed with additional diethyl ether. The combined filtrates were concentrated under vacuum to provide 4-chloro-3-methoxybenzaldehyde as a pale tan-yellow solid (630 mg, 87%). 1H NMR (400 MHz, CDCl3) δ ppm 3.98 (s, 3 H) 7.41 (dd, J=7.9, 1.8 Hz, 1 H) 7.45 (d, J=2.0 Hz, 1 H) 7.55 (d, J=7.6 Hz, 1 H) 9.95 (s, 1 H). was treated with Celite (2.0 g) the resulting mixture was stirred at rt for 3 h stirred vigorously The mixture was then filtered through a pad of silica gel the collected solids were rinsed with additional diethyl ether The combined filtrates were concentrated under vacuum

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

Procedure: A solution of 4-chloro-3-methoxybenzoic acid (1.12 g, 5.98 mmol) in THF (30 mL) was stirred on an ice bath and treated with a 1.0 M tetrahydrofuran solution of lithium aluminum hydride (7.18 mL, 7.18 mmol) over about a 5 min. period. The solution was stirred on ice for 2 h, and then quenched with rapid stirring by the slow dropwise addition of water (0.27 mL), followed by 15% aqueous sodium hydroxide (0.27 mL), then water (0.82 mL) again. Upon completion of addition, the resulting suspension was filtered and the collected solid was washed with ethyl acetate. The filtrate was concentrated under vacuum to provide (4-chloro-3-methoxyphenyl)methanol as a colorless oil (737 mg, 71%). 1H NMR (400 MHz, CDCl3) δ ppm 3.92 (s, 3 H) 4.67 (s, 2 H) 6.87 (d, J=7.6 Hz, 1 H) 6.98 (s, 1 H) 7.33 (d, J=7.6 Hz, 1 H). quenched with rapid stirring by the slow dropwise addition of water (0.27 mL) Upon completion of addition the resulting suspension was filtered the collected solid was washed with ethyl acetate The filtrate was concentrated under vacuum

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

Procedure: To a solution of (4-chloro-3-methoxyphenyl)methan-1-ol (5.08 g, 29.4 mmol) in benzene (120 mL) was added MnO2 (5.65 g, 65 mmol). The reaction mixture was refluxed for 17 hr, chilled, and filtered through Celite, washing the cake with CH2Cl2 (300 mL). The filtrate was concentrated in vacuo to give 4-chloro-3-methoxybenzaldehyde (4.5 g, 89%). The reaction mixture was refluxed for 17 hr chilled filtered through Celite washing the cake with CH2Cl2 (300 mL) The filtrate was concentrated in vacuo

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

Procedure: To a solution of 4-chloro-3-methoxybenzoic acid (4.88 g, 26.2 mmol) in THF (50 mL) was added borane-THF complex (52 mL 1M solution in THF, 52 mmol) via addition funnel over 10 min. The reaction mixture was refluxed for 2 hr, cooled, extracted with EtOAc, washed with water, 5% Na2CO3 and brine, dried and concentrated in vacuo to give (4-chloro-3-methoxyphenyl)methan-1-ol (4.5 g, 99%). ES-MS (M+H-H2O)+=155, 157 (Cl). via addition funnel over 10 min The reaction mixture was refluxed for 2 hr cooled extracted with EtOAc washed with water, 5% Na2CO3 and brine dried concentrated in vacuo

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

Procedure: To a solution of 4-chloro-3-methoxybenzoic acid (4.88 g, 26.2 mmol) in THF (50 mL) was added borane-THF complex (52 mL 1M solution in THF, 52 mmol) via addition funnel over 10 min. The reaction mixture was refluxed for 2 hr, cooled, extracted with EtOAc, washed with water, 5% Na2CO3 and brine, dried and concentrated in vacuo to give (4-chloro-3-methoxyphenyl)methan-1-ol (4.5 g, 99%). ES-MS (M+H-H2O)+=155, 157 (Cl). via addition funnel over 10 min The reaction mixture was refluxed for 2 hr cooled extracted with EtOAc washed with water, 5% Na2CO3 and brine dried concentrated in vacuo

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

Procedure: To a solution of (4-chloro-3-methoxyphenyl)methan-1-ol (5.08 g, 29.4 mmol) in benzene (120 mL) was added MnO2 (5.65 g, 65 mmol). The reaction mixture was refluxed for 17 hr, chilled, and filtered through Celite, washing the cake with CH2Cl2 (300 mL). The filtrate was concentrated in vacuo to give 4-chloro-3-methoxybenzaldehyde (4.5 g, 89%). The reaction mixture was refluxed for 17 hr chilled filtered through Celite washing the cake with CH2Cl2 (300 mL) The filtrate was concentrated in vacuo

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

Procedure: To a solution of (4-chloro-3-methoxyphenyl)methan-1-ol (5.08 g, 29.4 mmol) in benzene (120 mL) was added MnO2 (5.65 g, 65 mmol). The reaction mixture was refluxed for 17 hr, chilled, and filtered through Celite, washing the cake with CH2Cl2 (300 mL). The filtrate was concentrated in vacuo to give 4-chloro-3-methoxybenzaldehyde (4.5 g, 89%). The reaction mixture was refluxed for 17 hr chilled filtered through Celite washing the cake with CH2Cl2 (300 mL) The filtrate was concentrated in vacuo

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

Procedure: To a solution of 4-chloro-3-methoxybenzoic acid (4.88 g, 26.2 mmol) in THF (50 mL) was added borane-THF complex (52 mL 1M solution in THF, 52 mmol) via addition funnel over 10 min. The reaction mixture was refluxed for 2 hr, cooled, extracted with EtOAc, washed with water, 5% Na2CO3 and brine, dried and concentrated in vacuo to give (4-chloro-3-methoxyphenyl)methan-1-ol (4.5 g, 99%). ES-MS (M+H−H2O)+=155, 157 (Cl). via addition funnel over 10 min The reaction mixture was refluxed for 2 hr cooled extracted with EtOAc washed with water, 5% Na2CO3 and brine dried concentrated in vacuo

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

Procedure: To 30.6 ml of BH3.THF was added a solution of 3-methoxy-4-chlorobenzoic acid (35 g, 0.187 mol) in 450 ml of THF, and the mixture was refluxed with stirring under argon for 3 hours. The mixture was quenched with THF/water (1:1,300 ml), concentrated in vacuo, and the residue was partitioned between methylene chloride/water. The organic layer was dried over sodium sulfate and concentrated in vacuo to afford 29.4 g (90%) of 3-methoxy-4-chlorophenylmethanol. the mixture was refluxed The mixture was quenched with THF/water (1:1,300 ml) concentrated in vacuo the residue was partitioned between methylene chloride/water The organic layer was dried over sodium sulfate concentrated in vacuo

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

Procedure: To a solution of (4-chloro-3-methoxyphenyl)methan-1-ol (5.08 g, 29.4 mmol) in benzene (120 mL) was added MnO2 (5.65 g, 65 mmol). The reaction mixture was refluxed for 17 hr, chilled, and filtered through Celite, washing the cake with CH2Cl2 (300 mL). The filtrate was concentrated in vacuo to give 4-chloro-3-methoxybenzaldehyde (4.5 g, 89%). The reaction mixture was refluxed for 17 hr chilled filtered through Celite washing the cake with CH2Cl2 (300 mL) The filtrate was concentrated in vacuo

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

Procedure: To a solution of 4-chloro-3-methoxybenzoic acid (4.88 g, 26.2 mmol) in THF (50 mL) was added borane-THF complex (52 mL 1M solution in THF, 52 mmol) via addition funnel over 10 min. The reaction mixture was refluxed for 2 hr, cooled, extracted with EtOAc, washed with water, 5% Na2CO3 and brine, dried and concentrated in vacuo to give (4-chloro-3-methoxyphenyl)methan-1-ol (4.5 g, 99%). ES-MS (M+H−H2O)+=155, 157 (Cl). via addition funnel over 10 min The reaction mixture was refluxed for 2 hr cooled extracted with EtOAc washed with water, 5% Na2CO3 and brine dried concentrated in vacuo