叔-丁基-联苯-哌啶-4-yloxysilane

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Into a 250-mL round-bottom flask was placed a solution of piperidin-4-ol (4 g, 39.55 mmol, 1.00 equiv) in tetrahydrofuran (100 mL), TEA (12 g, 118.59 mmol, 3.00 equiv) and tert-butyl(chloro)diphenylsilane (16 g, 58.21 mmol, 1.47 equiv). The resulting solution was stirred for 16 h at room temperature. The solids were filtered out. The filtrate was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:2). Purification afforded 1.1 g (8%) of 4-[(tert-butyldiphenylsilyl)oxy]piperidine as a colorless oil. Into a 250-mL round-bottom flask was placed The solids were filtered out The filtrate was dried over anhydrous sodium sulfate concentrated under vacuum Purification

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 4-(tert-butyl-diphenyl-silanyloxy)-piperidine-1-carboxylic acid tert-butyl ester (54 mg, 0.124 mmol) was added 4M HCl/dioxane (2 mL) and CH2Cl2 (5 mL). The reaction mixture was stirred at RT for 2 h. 4M HCl/dioxane (3 mL) added and reaction stirred for a further 1 hr. The reaction mixture was concentrated in vacuo. The crude material was purified by silica gel column chromatography eluting with CH2Cl2 and increasing the polarity to 10% MeOH/CH2Cl2 to obtain 4-(tert-butyl-diphenyl silanyloxy)-piperidine as a cream foam (370 mg, 79%). reaction stirred for a further 1 hr The reaction mixture was concentrated in vacuo The crude material was purified by silica gel column chromatography eluting with CH2Cl2 increasing the polarity to 10% MeOH/CH2Cl2

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 4-(tert-butyl-diphenyl-silanyloxy)-piperidine-1-carboxylic acid tert-butyl ester (54 mg, 0.124 mmol) was added 4M HCl/dioxane (2 mL) and CH2Cl2 (5 mL). The reaction mixture was stirred at RT for 2 h. 4M HCl/dioxane (3 mL) added and reaction stirred for a further 1 hr. The reaction mixture was concentrated in vacuo. The crude material was purified by silica gel column chromatography eluting with CH2Cl2 and increasing the polarity to 10% MeOH/CH2Cl2 to obtain 4-(tert-butyl-diphenyl silanyloxy)-piperidine as a cream foam (370 mg, 79%). reaction stirred for a further 1 hr The reaction mixture was concentrated in vacuo The crude material was purified by silica gel column chromatography eluting with CH2Cl2 increasing the polarity to 10% MeOH/CH2Cl2

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A mixture of 500 mg (1.01 mmol) of the compound from Example 10A, 514 mg (1.51 mmol) of the compound from Example 9A, 92 mg (0.101 mmol) of tris(dibenzylideneacetone)dipalladium(0), 96 mg (0.202 mmol) of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-Phos) and 194 mg (2.02 mmol) of sodium tert-butoxide in 10 ml of toluene was heated to 80° C. under argon in a microwave oven (Biotage Initiator, dynamic control of the incident power) for 3 h. After cooling to RT, 100 ml of water were added to the reaction mixture, which was extracted three times with approx. 100 ml each time of ethyl acetate. The combined organic extracts were washed successively with water and saturated sodium chloride solution, dried over anhydrous magnesium sulphate, filtered and finally freed of the solvent on a rotary evaporator. The resulting crude product, which was the corresponding silyl-protected intermediate, was purified by means of MPLC (approx. 70 g of silica gel, eluent: cyclohexane→5:1 cyclohexane/ethyl acetate). Subsequently, this product was dissolved in 3.5 ml of THF, and 3.5 ml (3.5 mmol) of a 1 M solution of tetra-n-butylammonium fluoride (TBAF) in THF were added. After this mixture had been stirred at RT for 20 min, it was concentrated on a rotary evaporator. The title compound was isolated by means of MPLC (approx. 20 g of silica gel, eluent: 2:1→1:3 cyclohexane/ethyl acetate). After concentration and drying, the product was once again stirred with pentane/diethyl ether. 65 mg (12% of theory) of the title compound were thus obtained. After cooling to RT was extracted three times with approx. 100 ml each time of ethyl acetate The combined organic extracts were washed successively with water and saturated sodium chloride solution dried over anhydrous magnesium sulphate filtered finally freed of the solvent on a rotary evaporator was purified by means of MPLC (approx. 70 g of silica gel, eluent: cyclohexane→5:1 cyclohexane/ethyl acetate) Subsequently, this product was dissolved in 3.5 ml of THF 3.5 ml (3.5 mmol) of a 1 M solution of tetra-n-butylammonium fluoride (TBAF) in THF were added it was concentrated on a rotary evaporator

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Into a 250-mL round-bottom flask was placed a solution of piperidin-4-ol (4 g, 39.55 mmol, 1.00 equiv) in tetrahydrofuran (100 mL), TEA (12 g, 118.59 mmol, 3.00 equiv) and tert-butyl(chloro)diphenylsilane (16 g, 58.21 mmol, 1.47 equiv). The resulting solution was stirred for 16 h at room temperature. The solids were filtered out. The filtrate was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:2). Purification afforded 1.1 g (8%) of 4-[(tert-butyldiphenylsilyl)oxy]piperidine as a colorless oil. Into a 250-mL round-bottom flask was placed The solids were filtered out The filtrate was dried over anhydrous sodium sulfate concentrated under vacuum Purification

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To 4-(tert-butyl-diphenyl-silanyloxy)-piperidine-1-carboxylic acid tert-butyl ester (54 mg, 0.124 mmol) was added 4M HCl/dioxane (2 mL) and CH2Cl2 (5 mL). The reaction mixture was stirred at RT for 2 h. 4M HCl/dioxane (3 mL) added and reaction stirred for a further 1 hr. The reaction mixture was concentrated in vacuo. The crude material was purified by silica gel column chromatography eluting with CH2Cl2 and increasing the polarity to 10% MeOH/CH2Cl2 to obtain 4-(tert-butyl-diphenyl silanyloxy)-piperidine as a cream foam (370 mg, 79%). reaction stirred for a further 1 hr The reaction mixture was concentrated in vacuo The crude material was purified by silica gel column chromatography eluting with CH2Cl2 increasing the polarity to 10% MeOH/CH2Cl2