4-[tert-butyl(dimethyl)silyl]oxy-2-chlorobenzaldehyde

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

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

Procedure: To a stirred solution of 4-{[tert-butyl(dimethyl)silyl]oxy}-2-chlorobenzaldehyde (WO 2003051797, 1.58 g, 5.83 mmol) in methanol (5 mL) was added sodium borohydride (264 mg, 7.00 mmol) at 0° C. The mixture was stirred at room temperature for 3 h, and quenched by addition of aqueous ammonium chloride. The mixture was extracted with ethyl acetate (200 mL), and the organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was purified by column chromatography on silica gel (100 g) eluting with hexane/ethyl acetate (20/1 to 10/1) to afford 1.51 g (95%) of the title compound as a colorless oil: quenched by addition of aqueous ammonium chloride The mixture was extracted with ethyl acetate (200 mL) the organic layer was washed with brine dried over sodium sulfate evaporated The residue was purified by column chromatography on silica gel (100 g) eluting with hexane/ethyl acetate (20/1 to 10/1)

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

Procedure: A solution of 2-chloro-4-hydroxybenzaldehyde (5.0 g, 32 mmol), tert-butyl(dimethyl)silyl chloride (5.3 g, 35 mmol), imidazole (2.9 g, 45 mmol) and N,N-dimethylaminopyridine (10 mg) in N,N-dimethylformamide (40 ml) was stirred at room temperature under a nitrogen atmosphere for 16 hours. The solvent was removed in vacuo and the residue partitioned between ethyl acteate (100 ml) and water (100 ml). The organic phase was separated, washed with sat. aq. sodium chloride (50 ml), dried (sodium sulfate) and reduced in vacuo. Further purification by column chromatography on silica gel eluting with pentane:ethyl acetate (3:1 changing to 2:1) gave the title compound as a colourless oil (6.50 g). The solvent was removed in vacuo the residue partitioned between ethyl acteate (100 ml) and water (100 ml) The organic phase was separated washed with sat. aq. sodium chloride (50 ml) dried (sodium sulfate) Further purification by column chromatography on silica gel eluting with pentane:ethyl acetate (3:1 changing to 2:1)

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

Procedure: A solution of 2-chloro-4-hydroxybenzaldehyde (5.0 g, 32 mmol), tert-butyl(dimethyl)silyl chloride (5.3 g, 35 mmol), imidazole (2.9 g, 45 mmol) and N,N-dimethylaminopyridine (10 mg) in N,N-dimethylformamide (40 ml) was stirred at room temperature under a nitrogen atmosphere for 16 hours. The solvent was removed in vacuo and the residue partitioned between ethyl acteate (100 ml) and water (100 ml). The organic phase was separated, washed with sat. aq. sodium chloride (50 ml), dried (sodium sulfate) and reduced in vacuo. Further purification by column chromatography on silica gel eluting with pentane:ethyl acetate (3:1 changing to 2:1) gave the title compound as a colourless oil (6.50 g). The solvent was removed in vacuo the residue partitioned between ethyl acteate (100 ml) and water (100 ml) The organic phase was separated washed with sat. aq. sodium chloride (50 ml) dried (sodium sulfate) Further purification by column chromatography on silica gel eluting with pentane:ethyl acetate (3:1 changing to 2:1)

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

Procedure: A solution of 2-chloro-4-hydroxybenzaldehyde (5.0 g, 32 mmol), tert-butyl(dimethyl)silyl chloride (5.3 g, 35 mmol), imidazole (2.9 g, 45 mmol) and N,N-dimethylaminopyridine (10 mg) in N,N-dimethylformamide (40 ml) was stirred at room temperature under a nitrogen atmosphere for 16 hours. The solvent was removed in vacuo and the residue partitioned between ethyl acteate (100 ml) and water (100 ml). The organic phase was separated, washed with sat. aq. sodium chloride (50 ml), dried (sodium sulfate) and reduced in vacuo. Further purification by column chromatography on silica gel eluting with pentane:ethyl acetate (3:1 changing to 2:1) gave the title compound as a colourless oil (6.50 g). The solvent was removed in vacuo the residue partitioned between ethyl acteate (100 ml) and water (100 ml) The organic phase was separated washed with sat. aq. sodium chloride (50 ml) dried (sodium sulfate) Further purification by column chromatography on silica gel eluting with pentane:ethyl acetate (3:1 changing to 2:1)

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

Procedure: A solution of 2-chloro-4-hydroxybenzaldehyde (5.0 g, 32 mmol), tert-butyl(dimethyl)silyl chloride (5.3 g, 35 mmol), imidazole (2.9 g, 45 mmol) and N,N-dimethylaminopyridine (10 mg) in N,N-dimethylformamide (40 ml) was stirred at room temperature under a nitrogen atmosphere for 16 hours. The solvent was removed in vacuo and the residue partitioned between ethyl acteate (100 ml) and water (100 ml). The organic phase was separated, washed with sat. aq. sodium chloride (50 ml), dried (sodium sulfate) and reduced in vacuo. Further purification by column chromatography on silica gel eluting with pentane:ethyl acetate (3:1 changing to 2:1) gave the title compound as a colourless oil (6.50 g). The solvent was removed in vacuo the residue partitioned between ethyl acteate (100 ml) and water (100 ml) The organic phase was separated washed with sat. aq. sodium chloride (50 ml) dried (sodium sulfate) Further purification by column chromatography on silica gel eluting with pentane:ethyl acetate (3:1 changing to 2:1)

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

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

Procedure: A solution of 2-chloro-4-hydroxybenzaldehyde (5.0 g, 32 mmol), tert-butyl(dimethyl)silyl chloride (5.3 g, 35 mmol), imidazole (2.9 g, 45 mmol) and N,N-dimethylaminopyridine (10 mg) in N,N-dimethylformamide (40 mL) was stirred at room temperature for 16 hours. The solvent was removed in vacuo and the residue was partitioned between ethyl acetate (100 mL) and water (100 mL). The organic phase was separated, washed with brine (50 mL), dried over sodium sulfate and concentrated in vacuo. Purification by column chromatography on silica gel, eluting with pentane:ethyl acetate, 75:25 to 67:33, afforded the title compound as a colourless oil in 75% yield, 6.50 g. 1HNMR (400 MHz, CDCl3) δ: 0.25 (6H, s), 0.97 (9H, s), 6.80 (1H, dd), 6.87 (1H, d), 7.84 (1H, d), 10.32 (1H, s) The solvent was removed in vacuo the residue was partitioned between ethyl acetate (100 mL) and water (100 mL) The organic phase was separated washed with brine (50 mL) dried over sodium sulfate concentrated in vacuo Purification by column chromatography on silica gel eluting with pentane

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

Procedure: To a solution of 55% sodium hydride (128 mg) in tetrahydrofuran (15.0 mL) was added benzyl 2-(dimethoxyphosphoryl)propanoate (796 mg) under ice-cooling, followed by stirring for 30 minutes under ice-cooling. Subsequently, a solution of 4-{[tert-butyl(dimethyl)silyl]oxy}-2-chlorobenzaldehyde (720 mg) in tetrahydrofuran (3.00 mL) was added thereto, followed by stirring at room temperature for 4 hours. To the reaction mixture were added a saturated aqueous ammonium chloride solution, water, and ethyl acetate, and the organic layer was extracted. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To a solution of the residue in tetrahydrofuran (10.0 mL) was added a 1 M solution of tetra-n-butylammonium fluoride in tetrahydrofuran (2.70 mL) under ice-cooling, followed by stirring for 30 minutes under ice-cooling. After completion, to the reaction mixture were added a saturated aqueous ammonium chloride solution, water, and ethyl acetate, and the organic layer was extracted. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain benzyl (2E)-3-(2-chloro-4-hydroxyphenyl)-2-methylacrylate (587 mg). cooling cooling by stirring at room temperature for 4 hours the organic layer was extracted The organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure To a solution of the residue in tetrahydrofuran (10.0 mL) was added a 1 M solution of tetra-n-butylammonium fluoride in tetrahydrofuran (2.70 mL) under ice- cooling by stirring for 30 minutes under ice- cooling After completion, to the reaction mixture were added a saturated aqueous ammonium chloride solution, water, and ethyl acetate the organic layer was extracted The organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane-ethyl acetate)

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

Procedure: A solution of 2-chloro-4-hydroxybenzaldehyde (5.0 g, 32 mmol), tert-butyl(dimethyl)silyl chloride (5.3 g, 35 mmol), imidazole (2.9 g, 45 mmol) and N,N-dimethylaminopyridine (10 mg) in N,N-dimethylformamide (40 ml) was stirred at room temperature under a nitrogen atmosphere for 16 hours. The solvent was removed in vacuo and the residue partitioned between ethyl acteate (100 ml) and water (100 ml). The organic phase was separated, washed with sat. aq. sodium chloride (50 ml), dried (sodium sulfate) and reduced in vacuo. Further purification by column chromatography on silica gel eluting with pentane:ethyl acetate (3:1 changing to 2:1) gave the title compound as a colourless oil (6.50 g). The solvent was removed in vacuo the residue partitioned between ethyl acteate (100 ml) and water (100 ml) The organic phase was separated washed with sat. aq. sodium chloride (50 ml) dried (sodium sulfate) Further purification by column chromatography on silica gel eluting with pentane:ethyl acetate (3:1 changing to 2:1)

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

Procedure: A solution of 2-chloro-4-hydroxybenzaldehyde (5.0 g, 32 mmol), tert-butyl(dimethyl)silyl chloride (5.3 g, 35 mmol), imidazole (2.9 g, 45 mmol) and N,N-dimethylaminopyridine (10 mg) in N,N-dimethylformamide (40 mL) was stirred at room temperature for 16 hours. The solvent was removed in vacuo and the residue was partitioned between ethyl acetate (100 mL) and water (100 mL). The organic phase was separated, washed with brine (50 mL), dried over sodium sulfate and concentrated in vacuo. Purification by column chromatography on silica gel, eluting with pentane: ethyl acetate, 75:25 to 67:33, afforded the title compound as a colourless oil in 75% yield, 6.50 g. 1HNMR (400 MHz, CDCl3) δ: 0.25 (6H, s), 0.97 (9H, s), 6.80 (1H, dd), 6.87 (1H, d), 7.84 (1H, d), 10.32 (1H, s) The solvent was removed in vacuo the residue was partitioned between ethyl acetate (100 mL) and water (100 mL) The organic phase was separated washed with brine (50 mL) dried over sodium sulfate concentrated in vacuo Purification by column chromatography on silica gel eluting with pentane

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

Procedure: To a stirred solution of 4-{[tert-butyl(dimethyl)silyl]oxy}-2-chlorobenzaldehyde (WO 2003051797, 1.58 g, 5.83 mmol) in methanol (5 mL) was added sodium borohydride (264 mg, 7.00 mmol) at 0° C. The mixture was stirred at room temperature for 3 h, and quenched by addition of aqueous ammonium chloride. The mixture was extracted with ethyl acetate (200 mL), and the organic layer was washed with brine, dried over sodium sulfate, and evapolated. The residue was purified by column chromatography on silica gel (100 g) eluting with hexane/ethyl acetate (20/1 to 10/1) to afford 1.51 g (95%) of the title compound as a colorless oil: quenched by addition of aqueous ammonium chloride The mixture was extracted with ethyl acetate (200 mL) the organic layer was washed with brine dried over sodium sulfate The residue was purified by column chromatography on silica gel (100 g) eluting with hexane/ethyl acetate (20/1 to 10/1)