4,4-dimethylpentan-1-ol

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

Procedure: To a stirred solution of 4,4-dimethyl-pent-2-yn-1-ol (3.1 g, 27.6 mmol) in ethanol (30 ml) is added 10% palladium on carbon (0.3 g). The mixture is stirred under an atmosphere of hydrogen for 16 h. The reaction mixture is filtered through a pad of celite and the celite bed is washed with methanol (10 ml). The filtrate thus obtained is concentrated and the crude product is purified by column chromatography (5-10% ethyl acetate/hexane) to afford 4,4-dimethyl-pentan-1-ol and 4,4-dimethyl-pentan-1-al. To a stirred solution of 4,4-dimethyl-pentan-1-al (0.85 g, 7.45 mmol) in methanol (12 ml) is added sodium borohydride (0.56 g, 14.9 mmol) at 0° C. The reaction mixture is stirred at RT for 1.5 h. On completion, the solvent is evaporated and then diluted with ethyl acetate (30 ml). The organic layer is washed with water (2×20 ml), brine (20 ml), dried over sodium sulfate and concentrated affording 4,4-dimethyl-pentan-1-ol (1.52 g, 13.1 mmol, 48%). The reaction mixture is filtered through a pad of celite the celite bed is washed with methanol (10 ml) The filtrate thus obtained is concentrated the crude product is purified by column chromatography (5-10% ethyl acetate/hexane)

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

Procedure: To a stirred solution of 4,4-dimethyl-pent-2-yn-1-ol (3.1 g, 27.6 mmol) in ethanol (30 ml) is added 10% palladium on carbon (0.3 g). The mixture is stirred under an atmosphere of hydrogen for 16 h. The reaction mixture is filtered through a pad of celite and the celite bed is washed with methanol (10 ml). The filtrate thus obtained is concentrated and the crude product is purified by column chromatography (5-10% ethyl acetate/hexane) to afford 4,4-dimethyl-pentan-1-ol and 4,4-dimethyl-pentan-1-al. To a stirred solution of 4,4-dimethyl-pentan-1-al (0.85 g, 7.45 mmol) in methanol (12 ml) is added sodium borohydride (0.56 g, 14.9 mmol) at 0° C. The reaction mixture is stirred at RT for 1.5 h. On completion, the solvent is evaporated and then diluted with ethyl acetate (30 ml). The organic layer is washed with water (2×20 ml), brine (20 ml), dried over sodium sulfate and concentrated affording 4,4-dimethyl-pentan-1-ol (1.52 g, 13.1 mmol, 48%). The reaction mixture is filtered through a pad of celite the celite bed is washed with methanol (10 ml) The filtrate thus obtained is concentrated the crude product is purified by column chromatography (5-10% ethyl acetate/hexane)

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

Procedure: Intermediate 6 (2.12 g, 2.42 mmol, 1 eq.), 4,4-dimethyl-pentan-1-ol (0.77 g, 7.71 mmol, 1.2 eq.) and PPh3 (2.02 g, 7.71 mmol, 1.2 eq.) were suspended in 1,4-dioxane (50 mL) and the mixture was degassed with N2. DIAD (1.56 mL, 7.71 mmol, 1.1 eq.) was added dropwise and the reaction was stirred at RT for 2 h. The reaction mixture was quenched with brine and extracted with EtOAc, the organic phase was dried over MgSO4 and evaporated to dryness. Compound 143 was obtained by purification by flash chromatography on silica gel, eluting from 60 to 100% EtOAc/H. the mixture was degassed with N2 The reaction mixture was quenched with brine extracted with EtOAc the organic phase was dried over MgSO4 evaporated to dryness