5-[tert-butyl(dimethyl)silyl]oxypent-3-yn-2-one

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. solution of 2-cyanoacetamide (1.74 g, 20.7 mmol) and tBuOK (2.32 g, 20.7 mmol) in DMSO (48 mL) was added 5-{[tert-butyl(dimethyl)silyl]oxy}pent-3-yn-2-one (Cpd G, 4.4 g, 21.0 mmol) dropwise. The reaction mixture turned bright orange. The reaction mixture was stirred for 2 hours at 0° C., then quenched with NH4Cl (sat., aq.) and diluted with water causing solids to precipitate out. The solids were collected via filtration and dried under vacuum to give 4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (Cpd H, 5.0 g, 86%) as a tan solid. quenched with NH4Cl (sat., aq.) diluted with water causing solids to precipitate out The solids were collected via filtration dried under vacuum

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 0° C. solution of 2-cyanoacetamide (1.74 g, 20.7 mmol) and tBuOK (2.32 g, 20.7 mmol) in DMSO (48 mL) was added 5-{[tert-butyl(dimethyl)silyl]oxy}pent-3-yn-2-one (Cpd G, 4.4 g, 21.0 mmol) dropwise. The reaction mixture turned bright orange. The reaction mixture was stirred for 2 hours at 0° C., then quenched with NH4Cl (sat., aq.) and diluted with water causing solids to precipitate out. The solids were collected via filtration and dried under vacuum to give 4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (Cpd H, 5.0 g, 86%) as a tan solid. quenched with NH4Cl (sat., aq.) diluted with water causing solids to precipitate out The solids were collected via filtration dried under vacuum

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a −40° C. solution of tert-butyl(dimethyl)(prop-2-yn-1-yloxy)silane (1.70 g, 10 mmol) in THF (6 mL) was added iPrMgCl.LiCl (8.46 mL, 11 mmol) dropwise keeping the internal temperature below −20° C. A solution of the N-methoxy-N-methylacetamide (1.13 g, 11.0 mmol) in THF (4 mL) was cooled to −10° C. and the alkyne solution was added to the Weinreb amide solution via cannula. The reaction mixture was stirred at −10° C. for 10 minutes. The reaction mixture was poured into a mixture of saturated NH4Cl and ice. The aqueous layer was extracted with EtOAc. The organic layer was washed with brine, dried with Mg2SO4, filtered, then concentrated under vacuum to give 5-{[tert-butyl(dimethyl)silyl]oxy}pent-3-yn-2-one (Cpd G, 1.5 g, 64%) as an oil. the internal temperature below −20° C The aqueous layer was extracted with EtOAc The organic layer was washed with brine dried with Mg2SO4 filtered concentrated under vacuum

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

Procedure: To a stirred solution of compound 5-((tert-butyldimethylsilyl)oxy)pent-3-yn-2-one (13.0 g, 61.0 mmol) and cyanoacetamide (6.2 g, 73.2 mmol) in a mixture of ethanol and water (9:1) (270 mL) at room temperature was added piperidineacetate (catalytic) and the reaction mixture was heated to reflux for 5 h. After removal of solvent water was added and the solid product was filtered. The solid product on washing with water followed by ether and hexane afforded the desired compound (5.5 g, 32%). the reaction mixture was heated to reflux for 5 h After removal of solvent water was added the solid product was filtered The solid product on washing with water

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

Procedure: To a stirred solution of tert-butyldimethyl(prop-2-yn-1-yloxy)silane (20.0 g, 116.9 mmol) in THF (400 mL) at −78° C. was added n-BuLi (90 mL, 140.0 mmol) and the reaction mixture was allowed to attain room temperature with in 2 h. Then the reaction mixture was cooled to −78° C. and borontrifluoride etherate (18 mL, 140.0 mmol) was added. After 10 minutes stirring acetic anhydride (15 mL, 153.0 mmol) was added and the reaction mixture was allowed to attain room temperature with in 2.5 h. Reaction was quenched with aqueous 1N NaOH solution and extracted with ethyl acetate (3 times). Combined organic layer was dried over sodium sulphate. Removal of the solvent under reduced pressure followed by solvent washings afforded C (13 g, 52%). to attain room temperature with in 2 h was added to attain room temperature with in 2.5 h Reaction was quenched with aqueous 1N NaOH solution extracted with ethyl acetate (3 times) Combined organic layer was dried over sodium sulphate Removal of the solvent under reduced pressure afforded C (13 g, 52%)

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyldimethyl(prop-2-yn-1-yloxy)silane (15.1 g, 88.3%) in THF (300 mL), n-BuLi (67 mL, 105.9 mmol, 1.6 N in hexane) was added slowly at −78° C. After the addition was complete, the temperature was increased slowly to 10° C. over a period of 2 h. The reaction mixture was cooled again to −78° C. and BF3.OEt2 (14 mL, 105.9 mmol) added slowly and reaction mixture stirred at this temperature for 5 min. Acetic anhydride (11 mL, 115.6 mmol) was slowly added and the reaction was continued while temperature was allowed to rise to room temperature over a period of 2 h. After this time, reaction mass was quenched with 1N NaOH till pH 7-8 and biphasic solution was extracted with ethyl acetate. The organic layer was concentrated to obtain crude material which was further purified by column chromatography over silica gel to yield 5-((tert-butyldimethylsilyl)oxy)pent-3-yn-2-one (9.2 g, 52.6%). After the addition The reaction mixture was cooled again to −78° C. reaction mixture to rise to room temperature over a period of 2 h After this time, reaction mass was quenched with 1N NaOH till pH 7-8 and biphasic solution was extracted with ethyl acetate The organic layer was concentrated to obtain crude material which was further purified by column chromatography over silica gel

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of tert-butyldimethyl(prop-2-yn-1-yloxy)silane (15.1 g, 88.3%) in THF (300 mL), n-BuLi (67 mL, 105.9 mmol, 1.6 N in hexane) was added slowly at −78° C. After the addition was complete, the temperature was increased slowly to 10° C. over a period of 2 h. The reaction mixture was cooled again to −78° C. and BF3.OEt2 (14 mL, 105.9 mmol) added slowly and reaction mixture stirred at this temperature for 5 min. Acetic anhydride (11 mL, 115.6 mmol) was slowly added and the reaction was continued while temperature was allowed to rise to room temperature over a period of 2 h. After this time, reaction mass was quenched with 1N NaOH till pH 7-8 and biphasic solution was extracted with ethyl acetate. The organic layer was concentrated to obtain crude material which was further purified by column chromatography over silica gel to yield 5-((tert-butyldimethylsilyl)oxy)pent-3-yn-2-one (9.2 g, 52.6%). After the addition The reaction mixture was cooled again to −78° C. reaction mixture to rise to room temperature over a period of 2 h After this time, reaction mass was quenched with 1N NaOH till pH 7-8 and biphasic solution was extracted with ethyl acetate The organic layer was concentrated to obtain crude material which was further purified by column chromatography over silica gel

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

Procedure: To a stirred solution of compound 5-((tert-butyldimethylsilyl)oxy)pent-3-yn-2-one (13.0 g, 61.0 mmol) and cyanoacetamide (6.2 g, 73.2 mmol) in a mixture of ethanol and water (9:1) (270 mL) at room temperature was added piperidineacetate (catalytic) and the reaction mixture was heated to reflux for 5 h. After removal of solvent water was added and the solid product was filtered. The solid product on washing with water followed by ether and hexane afforded the desired compound (5.5 g, 32%). the reaction mixture was heated to reflux for 5 h After removal of solvent water was added the solid product was filtered The solid product on washing with water

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

Procedure: To a stirred solution of tert-butyldimethyl(prop-2-yn-1-yloxy)silane (20.0 g, 116.9 mmol) in THF (400 mL) at −78° C. was added n-BuLi (90 mL, 140.0 mmol) and the reaction mixture was allowed to attain room temperature with in 2 h. Then the reaction mixture was cooled to −78° C. and borontrifluoride etherate (18 mL, 140.0 mmol) was added. After 10 minutes stirring acetic anhydride (15 mL, 153.0 mmol) was added and the reaction mixture was allowed to attain room temperature with in 2.5 h. Reaction was quenched with aqueous 1N NaOH solution and extracted with ethyl acetate (3 times). Combined organic layer was dried over sodium sulphate. Removal of the solvent under reduced pressure followed by solvent washings afforded C (13 g, 52%). to attain room temperature with in 2 h was added to attain room temperature with in 2.5 h Reaction was quenched with aqueous 1N NaOH solution extracted with ethyl acetate (3 times) Combined organic layer was dried over sodium sulphate Removal of the solvent under reduced pressure afforded C (13 g, 52%)

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

Procedure: To a stirred solution of compound 5-((tert-butyldimethylsilyl)oxy)pent-3-yn-2-one (13.0 g, 61.0 mmol) and cyanoacetamide (6.2 g, 73.2 mmol) in a mixture of ethanol and water (9:1) (270 mL) at room temperature was added piperidineacetate (catalytic) and the reaction mixture was heated to reflux for 5 h. After removal of solvent water was added and the solid product was filtered. The solid product on washing with water followed by ether and hexane afforded the desired compound (5.5 g, 32%). the reaction mixture was heated to reflux for 5 h After removal of solvent water was added the solid product was filtered The solid product on washing with water

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

Procedure: To a stirred solution of tert-butyldimethyl(prop-2-yn-1-yloxy)silane (20.0 g, 116.9 mmol) in THF (400 mL) at −78° C. was added n-BuLi (90 mL, 140.0 mmol) and the reaction mixture was allowed to attain room temperature with in 2 h. Then the reaction mixture was cooled to −78° C. and borontrifluoride etherate (18 mL, 140.0 mmol) was added. After 10 minutes stirring acetic anhydride (15 mL, 153.0 mmol) was added and the reaction mixture was allowed to attain room temperature with in 2.5 h. Reaction was quenched with aqueous 1N NaOH solution and extracted with ethyl acetate (3 times). Combined organic layer was dried over sodium sulphate. Removal of the solvent under reduced pressure followed by solvent washings afforded C (13 g, 52%). to attain room temperature with in 2 h was added to attain room temperature with in 2.5 h Reaction was quenched with aqueous 1N NaOH solution extracted with ethyl acetate (3 times) Combined organic layer was dried over sodium sulphate Removal of the solvent under reduced pressure afforded C (13 g, 52%)