6-chloro-2,2-dimethyl-3,4-dihydrochromene-8-carbaldehyde

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

Procedure: Using essentially the same procedure as Example 5-22, Step 4, Pd(OAc)2 (7.04 mg, 0.03 mmol), X-Phos (29.9 mg, 0.06 mmol), potassium carbonate (434 mg, 3.14 mmol), potassium cyclopropyltrifluoroborate (170 mg, 1.15 mmol) and 6-chloro-2,2-dimethyl-3,4-dihydro-2H-chromene-8-carbaldehyde (235 mg, 1.05 mmol, Example 5-26, Step 3) afforded the desired product as a pale-yellow oil.

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

Procedure: 6-Chloro-2,2-dimethyl-3,4-dihydro-2H-chromene-8-carboxylate (350 mg, 1.37 mmol) was dissolved in dichloromethane (6.87 mL) and cooled to −78° C. DIBAL-H (4.12 mL, 4.12 mmol) was added dropwise. The reaction mixture was warmed to room temperature and stirred for 1 hour. It was then cooled to 0° C., diluted with dichloromethane (10.0 mL) and water (2.00 mL) was added slowly, followed by a 15% aqueous NaOH solution (5.00 mL). The mixture was warmed to room temperature and stirred for 15 minutes. The organic layer was separated, dried over Na2SO4, filtered, and concentrated under vacuum. The crude alcohol was used directly in the next step without further purification. The crude alcohol was dissolved in dichloromethane (7.00 mL), and Dess-Martin periodinane (1.20 g, 2.75 mmol) was added in one portion at room temperature. The reaction mixture was stirred at room temperature for 30 minutes and then concentrated under vacuum on silica gel. It was then purified by silica gel chromatography eluting with 0-15% EtOAc/hexanes to give the desired product as a white solid. The reaction mixture was warmed to room temperature It was then cooled to 0° C. was added slowly The mixture was warmed to room temperature stirred for 15 minutes The organic layer was separated dried over Na2SO4 filtered concentrated under vacuum The crude alcohol was used directly in the next step without further purification The crude alcohol was dissolved in dichloromethane (7.00 mL) The reaction mixture was stirred at room temperature for 30 minutes concentrated under vacuum on silica gel It was then purified by silica gel chromatography eluting with 0-15% EtOAc/hexanes

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

Procedure: Using essentially the same procedure as Example 5-22, Step 4, Pd(OAc)2 (7.04 mg, 0.03 mmol), X-Phos (29.9 mg, 0.06 mmol), potassium carbonate (434 mg, 3.14 mmol), potassium cyclopropyltrifluoroborate (170 mg, 1.15 mmol) and 6-chloro-2,2-dimethyl-3,4-dihydro-2H-chromene-8-carbaldehyde (235 mg, 1.05 mmol, Example 5-26, Step 3) afforded the desired product as a pale-yellow oil.

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

Procedure: Using essentially the same procedure as Example 5-22, Step 4, Pd(OAc)2 (7.04 mg, 0.03 mmol), X-Phos (29.9 mg, 0.06 mmol), potassium carbonate (434 mg, 3.14 mmol), potassium cyclopropyltrifluoroborate (170 mg, 1.15 mmol) and 6-chloro-2,2-dimethyl-3,4-dihydro-2H-chromene-8-carbaldehyde (235 mg, 1.05 mmol, Example 5-26, Step 3) afforded the desired product as a pale-yellow oil.

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

Procedure: 6-Chloro-2,2-dimethyl-3,4-dihydro-2H-chromene-8-carboxylate (350 mg, 1.37 mmol) was dissolved in dichloromethane (6.87 mL) and cooled to −78° C. DIBAL-H (4.12 mL, 4.12 mmol) was added dropwise. The reaction mixture was warmed to room temperature and stirred for 1 hour. It was then cooled to 0° C., diluted with dichloromethane (10.0 mL) and water (2.00 mL) was added slowly, followed by a 15% aqueous NaOH solution (5.00 mL). The mixture was warmed to room temperature and stirred for 15 minutes. The organic layer was separated, dried over Na2SO4, filtered, and concentrated under vacuum. The crude alcohol was used directly in the next step without further purification. The crude alcohol was dissolved in dichloromethane (7.00 mL), and Dess-Martin periodinane (1.20 g, 2.75 mmol) was added in one portion at room temperature. The reaction mixture was stirred at room temperature for 30 minutes and then concentrated under vacuum on silica gel. It was then purified by silica gel chromatography eluting with 0-15% EtOAc/hexanes to give the desired product as a white solid. The reaction mixture was warmed to room temperature It was then cooled to 0° C. was added slowly The mixture was warmed to room temperature stirred for 15 minutes The organic layer was separated dried over Na2SO4 filtered concentrated under vacuum The crude alcohol was used directly in the next step without further purification The crude alcohol was dissolved in dichloromethane (7.00 mL) The reaction mixture was stirred at room temperature for 30 minutes concentrated under vacuum on silica gel It was then purified by silica gel chromatography eluting with 0-15% EtOAc/hexanes

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

Procedure: 6-Chloro-2,2-dimethyl-3,4-dihydro-2H-chromene-8-carboxylate (350 mg, 1.37 mmol) was dissolved in dichloromethane (6.87 mL) and cooled to −78° C. DIBAL-H (4.12 mL, 4.12 mmol) was added dropwise. The reaction mixture was warmed to room temperature and stirred for 1 hour. It was then cooled to 0° C., diluted with dichloromethane (10.0 mL) and water (2.00 mL) was added slowly, followed by a 15% aqueous NaOH solution (5.00 mL). The mixture was warmed to room temperature and stirred for 15 minutes. The organic layer was separated, dried over Na2SO4, filtered, and concentrated under vacuum. The crude alcohol was used directly in the next step without further purification. The crude alcohol was dissolved in dichloromethane (7.00 mL), and Dess-Martin periodinane (1.20 g, 2.75 mmol) was added in one portion at room temperature. The reaction mixture was stirred at room temperature for 30 minutes and then concentrated under vacuum on silica gel. It was then purified by silica gel chromatography eluting with 0-15% EtOAc/hexanes to give the desired product as a white solid. The reaction mixture was warmed to room temperature It was then cooled to 0° C. was added slowly The mixture was warmed to room temperature stirred for 15 minutes The organic layer was separated dried over Na2SO4 filtered concentrated under vacuum The crude alcohol was used directly in the next step without further purification The crude alcohol was dissolved in dichloromethane (7.00 mL) The reaction mixture was stirred at room temperature for 30 minutes concentrated under vacuum on silica gel It was then purified by silica gel chromatography eluting with 0-15% EtOAc/hexanes

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

Procedure: Using essentially the same procedure as Example 5-22, Step 4, Pd(OAc)2 (7.04 mg, 0.03 mmol), X-Phos (29.9 mg, 0.06 mmol), potassium carbonate (434 mg, 3.14 mmol), potassium cyclopropyltrifluoroborate (170 mg, 1.15 mmol) and 6-chloro-2,2-dimethyl-3,4-dihydro-2H-chromene-8-carbaldehyde (235 mg, 1.05 mmol, Example 5-26, Step 3) afforded the desired product as a pale-yellow oil.

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

Procedure: 6-Chloro-2,2-dimethyl-3,4-dihydro-2H-chromene-8-carboxylate (350 mg, 1.37 mmol) was dissolved in dichloromethane (6.87 mL) and cooled to −78° C. DIBAL-H (4.12 mL, 4.12 mmol) was added dropwise. The reaction mixture was warmed to room temperature and stirred for 1 hour. It was then cooled to 0° C., diluted with dichloromethane (10.0 mL) and water (2.00 mL) was added slowly, followed by a 15% aqueous NaOH solution (5.00 mL). The mixture was warmed to room temperature and stirred for 15 minutes. The organic layer was separated, dried over Na2SO4, filtered, and concentrated under vacuum. The crude alcohol was used directly in the next step without further purification. The crude alcohol was dissolved in dichloromethane (7.00 mL), and Dess-Martin periodinane (1.20 g, 2.75 mmol) was added in one portion at room temperature. The reaction mixture was stirred at room temperature for 30 minutes and then concentrated under vacuum on silica gel. It was then purified by silica gel chromatography eluting with 0-15% EtOAc/hexanes to give the desired product as a white solid. The reaction mixture was warmed to room temperature It was then cooled to 0° C. was added slowly The mixture was warmed to room temperature stirred for 15 minutes The organic layer was separated dried over Na2SO4 filtered concentrated under vacuum The crude alcohol was used directly in the next step without further purification The crude alcohol was dissolved in dichloromethane (7.00 mL) The reaction mixture was stirred at room temperature for 30 minutes concentrated under vacuum on silica gel It was then purified by silica gel chromatography eluting with 0-15% EtOAc/hexanes