4-chloro-2-hydroxy-6-methoxybenzaldehyde

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of 4-chloro-2-hydroxy-6-methoxybenzaldehyde (Example 37B, 1.79 g, 9.59 mmol) in N,N-dimethylformamide (15 mL, 9.59 mmol) was charged with cesium carbonate (3.75 g, 11.51 mmol) and 1-chloropropan-2-one (0.975 mL, 11.51 mmol). The reaction mixture was heated in a sealable vessel at 65° C. for 7 hours, was filtered over a Whatman filter paper to remove insolubles rinsing with DCM then washed with sat. NaHCO3. The organic phase was dried (MgSO4), filtered and concentrated to dryness. The residue was purified by ISCO using hexanes/EtOAc as eluent. Fractions containing the desired product were concentrated to give the title material (1.43 g, 6.37 mmol, 66% yield) as a light yellow solid. LC (Method A): 1.952 min. LCMS (APCI) calcd for C11H10ClO3 [M+H]+ m/z 225.03, found 225.0. 1H NMR (CDCl3, 400 MHz) δ ppm: 7.94 (d, J=0.8 Hz, 1H), 7.49 (dd, J=0.8, 1.6 Hz, 1H), 6.97 (d, J=1.6 Hz, 1H), 3.97 (s, 3H). was filtered over a Whatman filter paper to remove insolubles rinsing with DCM then washed with sat. NaHCO3 The organic phase was dried (MgSO4) filtered concentrated to dryness The residue was purified by ISCO Fractions containing the desired product were concentrated

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of 4-chloro-2-hydroxy-6-methoxybenzaldehyde (Example 37B, 1.79 g, 9.59 mmol) in N,N-dimethylformamide (15 mL, 9.59 mmol) was charged with cesium carbonate (3.75 g, 11.51 mmol) and 1-chloropropan-2-one (0.975 mL, 11.51 mmol). The reaction mixture was heated in a sealable vessel at 65° C. for 7 hours, was filtered over a Whatman filter paper to remove insolubles rinsing with DCM then washed with sat. NaHCO3. The organic phase was dried (MgSO4), filtered and concentrated to dryness. The residue was purified by ISCO using hexanes/EtOAc as eluent. Fractions containing the desired product were concentrated to give the title material (1.43 g, 6.37 mmol, 66% yield) as a light yellow solid. LC (Method A): 1.952 min. LCMS (APCI) calcd for C11H10ClO3 [M+H]+ m/z 225.03, found 225.0. 1H NMR (CDCl3, 400 MHz) δ ppm: 7.94 (d, J=0.8 Hz, 1H), 7.49 (dd, J=0.8, 1.6 Hz, 1H), 6.97 (d, J=1.6 Hz, 1H), 3.97 (s, 3H). was filtered over a Whatman filter paper to remove insolubles rinsing with DCM then washed with sat. NaHCO3 The organic phase was dried (MgSO4) filtered concentrated to dryness The residue was purified by ISCO Fractions containing the desired product were concentrated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of 4-chloro-2,6-dimethoxybenzaldehyde (Example 37A, 1.95 g, 9.72 mmol) in DCM (20 mL, 311 mmol) at −78° C. was slowly added boron tribromide (9.72 mL, 9.72 mmol). The reaction mixture was stirred at −78° C. for 10 minutes then warmed to r.t. and stirred for 1 hour while monitoring reaction progress by LCMS. Once all s.m. had been consumed, the reaction was quenched with water and extracted with DCM. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to dryness to give the title material (1.79 g, 9.59 mmol, 99% yield) as a purple solid. LC (Method B): 2.199 min. LCMS (APCI) calcd for C8H8ClO3 [M+H]+ m/z 187.02, found 187.0. 1H NMR (CDCl3, 400 MHz) δ ppm: 11.89 (s, 1H), 10.20 (s, 1H), 6.75 (t, J=2.0 Hz, 1H), 6.66 (m, 1H), 3.91 (s, 1H). at −78° C. then warmed to r.t. stirred for 1 hour reaction progress by LCMS had been consumed the reaction was quenched with water extracted with DCM The organic phase was washed with brine dried (MgSO4) filtered concentrated to dryness

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of 4-chloro-2-hydroxy-6-methoxybenzaldehyde (Example 37B, 1.79 g, 9.59 mmol) in N,N-dimethylformamide (15 mL, 9.59 mmol) was charged with cesium carbonate (3.75 g, 11.51 mmol) and 1-chloropropan-2-one (0.975 mL, 11.51 mmol). The reaction mixture was heated in a sealable vessel at 65° C. for 7 hours, was filtered over a Whatman filter paper to remove insolubles rinsing with DCM then washed with sat. NaHCO3. The organic phase was dried (MgSO4), filtered and concentrated to dryness. The residue was purified by ISCO using hexanes/EtOAc as eluent. Fractions containing the desired product were concentrated to give the title material (1.43 g, 6.37 mmol, 66% yield) as a light yellow solid. LC (Method A): 1.952 min. LCMS (APCI) calcd for C11H10ClO3 [M+H]+ m/z 225.03. found 225.0. 1H NMR (CDCl3, 400 MHz) δ ppm: 7.94 (d, J=0.8 Hz, 1H), 7.49 (dd, J=0.8, 1.6 Hz, 1H), 6.97 (d, J=1.6 Hz, 1H), 3.97 (s, 3H). was filtered over a Whatman filter paper to remove insolubles rinsing with DCM then washed with sat. NaHCO3 The organic phase was dried (MgSO4) filtered concentrated to dryness The residue was purified by ISCO Fractions containing the desired product were concentrated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of 4-chloro-2,6-dimethoxybenzaldehyde (Example 37A, 1.95 g, 9.72 mmol) in DCM (20 mL, 311 mmol) at −78° C. was slowly added boron tribromide (9.72 mL, 9.72 mmol). The reaction mixture was stirred at −78° C. for 10 minutes then warmed to r.t. and stirred for 1 hour while monitoring reaction progress by LCMS. Once all s.m. had been consumed, the reaction was quenched with water and extracted with DCM. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to dryness to give the title material (1.79 g, 9.59 mmol, 99% yield) as a purple solid. LC (Method B): 2.199 min. LCMS (APCI) calcd for C8H8ClO3 [M+H]+ m/z 187.02. found 187.0. 1H NMR (CDCl3, 400 MHz) δ ppm: 11.89 (s, 1H), 10.20 (s, 1H), 6.75 (t, J=2.0 Hz, 1H), 6.66 (m, 1H), 3.91 (s, 1H). at −78° C. then warmed to r.t. stirred for 1 hour reaction progress by LCMS had been consumed the reaction was quenched with water extracted with DCM The organic phase was washed with brine dried (MgSO4) filtered concentrated to dryness

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of 4-chloro-2-hydroxy-6-methoxybenzaldehyde (Example 37B, 1.79 g, 9.59 mmol) in N,N-dimethylformamide (15 mL, 9.59 mmol) was charged with cesium carbonate (3.75 g, 11.51 mmol) and 1-chloropropan-2-one (0.975 mL, 11.51 mmol). The reaction mixture was heated in a sealable vessel at 65° C. for 7 hours, was filtered over a Whatman filter paper to remove insolubles rinsing with DCM then washed with sat. NaHCO3. The organic phase was dried (MgSO4), filtered and concentrated to dryness. The residue was purified by ISCO using hexanes/EtOAc as eluent. Fractions containing the desired product were concentrated to give the title material (1.43 g, 6.37 mmol, 66% yield) as a light yellow solid. LC (Method A): 1.952 min. LCMS (APCI) calcd for C11H10ClO3 [M+H]+ m/z 225.03, found 225.0. 1H NMR (CDCl3, 400 MHz) δ ppm: 7.94 (d, J=0.8 Hz, 1H), 7.49 (dd, J=0.8, 1.6 Hz, 1H), 6.97 (d, J=1.6 Hz, 1H), 3.97 (s, 3H). was filtered over a Whatman filter paper to remove insolubles rinsing with DCM then washed with sat. NaHCO3 The organic phase was dried (MgSO4) filtered concentrated to dryness The residue was purified by ISCO Fractions containing the desired product were concentrated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of 4-chloro-2,6-dimethoxybenzaldehyde (Example 37A, 1.95 g, 9.72 mmol) in DCM (20 mL, 311 mmol) at −78° C. was slowly added boron tribromide (9.72 mL, 9.72 mmol). The reaction mixture was stirred at −78° C. for 10 minutes then warmed to r.t. and stirred for 1 hour while monitoring reaction progress by LCMS. Once all s.m. had been consumed, the reaction was quenched with water and extracted with DCM. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to dryness to give the title material (1.79 g, 9.59 mmol, 99% yield) as a purple solid. LC (Method B): 2.199 min. LCMS (APCI) calcd for C8H8ClO3 [M+H]+ m/z 187.02, found 187.0. 1H NMR (CDCl3, 400 MHz) δ ppm: 11.89 (s, 1H), 10.20 (s, 1H), 6.75 (t, J=2.0 Hz, 1H), 6.66 (m, 1H), 3.91 (s, 1H). at −78° C. then warmed to r.t. stirred for 1 hour reaction progress by LCMS had been consumed the reaction was quenched with water extracted with DCM The organic phase was washed with brine dried (MgSO4) filtered concentrated to dryness