4-chloro-3-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:; 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 heterogenous mixture of methanol (2 ml), CH2Cl2 (3 ml), 4-chloro-3-methoxybenzaldehyde (2 g, 11.7 mmol; prepared essentially as described by R. M. Riggs et al., J. Med. Chem., 30 1887, 1987.), trimethyl orthoformate (1.7 ml, 15.5 mmol) and a large crystal of p-toluenesulfonic acid was stirred at room temperature for one hour. Additional MeOH (1 ml) and a crystal of p-toluenesulfonic acid were added and the solution was warmed until homogenous. Upon completion of the reaction, the solution was stirred 5 min with excess solid NaHCO3 and rotory evaporated to remove solvents. The paste was dissolved in 40 ml EtOAC, partitioned against dilute NaHCO3 solution, and evaporated to yield a light brown oil. The reaction was repeated with another 2 g of 4-chloro-3-methoxybenzaldehyde and both product oils were combined to give 4.37 g (86%) of dimethyl acetal 3. prepared essentially the solution was warmed until homogenous Upon completion of the reaction evaporated to remove solvents The paste was dissolved in 40 ml EtOAC partitioned against dilute NaHCO3 solution evaporated to yield a light brown oil

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

Procedure: A heterogenous mixture of methanol (2 ml), CH2Cl2 (3 ml), 4-chloro-3-methoxybenzaldehyde (2 g, 11.7 mmol; prepared essentially as described by R. M. Riggs et al., J. Med. Chem., 30 1887, 1987.), trimethyl orthoformate (1.7 ml, 15.5 mmol) and a large crystal of p-toluenesulfonic acid was stirred at room temperature for one hour. Additional MeOH (1 ml) and a crystal of p-toluenesulfonic acid were added and the solution was warmed until homogenous. Upon completion of the reaction, the solution was stirred 5 min with excess solid NaHCO3 and rotory evaporated to remove solvents. The paste was dissolved in 40 ml EtOAC, partitioned against dilute NaHCO3 solution, and evaporated to yield a light brown oil. The reaction was repeated with another 2 g of 4-Chloro-3-methyoxybenzaldehyde and both product oils were combined to give 4.37 g (86%) of dimethyl acetal 3. prepared essentially the solution was warmed until homogenous Upon completion of the reaction evaporated to remove solvents The paste was dissolved in 40 ml EtOAC partitioned against dilute NaHCO3 solution evaporated to yield a light brown oil

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-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: Ceric ammonium nitrate (43.3 g, 79.0 mmol, 4.00 equiv) was dissolved in 1:1 HOAc/H2O (200 mL). This solution was added dropwise over one hour to a stirred solution of the product from Step 1 (3.09 g, 19.7 mmol, 1.00 equiv) in 1:1 HOAc/H2O (100 mL) at 100° C. After the addition was complete, the reaction was stirred for an additional 15 minutes. The reaction was cooled, diluted with H2O and extracted twice with Et2O. The combined organic extracts were washed three times with H2O, three times with satd. NaHCO3, and once with brine. The organic phase was dried over MgSO4 and concentrated en vacuo to afford the title compound (3.00 g, 89%) as an amber oil. 1H NMR (400 MHz, CDCL3) 9.97 (s, 1H), 7.57 (d, 1H), 7.46 (s, 1H), 7.43 (d, 1H), 4.00 (s, 3H). After the addition The reaction was cooled extracted twice with Et2O The combined organic extracts were washed three times with H2O, three times with satd The organic phase was dried over MgSO4 concentrated en vacuo

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

Procedure: Ceric ammonium nitrate (43.3 g, 79.0 mmol, 4.00 equiv) was dissolved in 1:1 HOAc/H2O (200 mL). This solution was added dropwise over one hour to a stirred solution of the product from Step 1 (3.09 g, 19.7 mmol, 1.00 equiv) in 1:1 HOAc/H2O (100 mL) at 100° C. After the addition was complete, the reaction was stirred for an additional 15 minutes. The reaction was cooled, diluted with H2O and extracted twice with Et2O. The combined organic extracts were washed three times with H2O, three times with satd. NaHCO3, and once with brine. The organic phase was dried over MgSO4 and concentrated en vacuo to afford the title compound (3.00 g, 89%) as an amber oil. 1H NMR (400 MHz, CDCL3) 9.97 (s, 1H), 7.57 (d, 1H), 7.46 (s, 1H), 7.43 (d, 1H), 4.00 (s, 3H). After the addition The reaction was cooled extracted twice with Et2O The combined organic extracts were washed three times with H2O, three times with satd The organic phase was dried over MgSO4 concentrated en 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