5-[(4-hydroxyphenyl)methylidene]-2,2-dimethyl-1,3-dioxane-4,6-dione

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

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

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

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-propynyl magnesium bromide in THF (0.5 N, 322 mL, 161.28 mmol) is added a solution of 5-(4-hydroxy-benzylidene)-2,2-dimethyl-[1,3]dioxane-4,6-dione (20 g, 80.64 mmol) in THF (200 mL) by cannula under a nitrogen atmosphere. Over the course of the addition, the reaction mixture changed to a thick, yellow suspension. After addition is compete, the reaction mixture is stirred for 15 minutes at 50° C., quenched with aqueous NH4Cl, and acidified to pH ˜2 with 2 N HCl. The mixture is extracted with EtOAc (2×300 mL) and the combined extracts are washed with saturated brine, dried over MgSO4, filtered, and concentrated to a yellow solid (20 g, 86%). The product is carried on crude. Over the course of the addition After addition quenched with aqueous NH4Cl The mixture is extracted with EtOAc (2×300 mL) the combined extracts are washed with saturated brine dried over MgSO4 filtered concentrated to a yellow solid (20 g, 86%)

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

Procedure: To a solution of 4-hydroxybenzaldehyde (20 g, 163 mmol) in water (250 mL) is added Meldrum's acid (2,2-dimethyl-1,3-dioxane-4,6-dione) (24.78 g, 171 mmol) as a slurry in water (250 mL) at 75° C. The reaction mixture is agitated for 2 hours, cooled in an ice bath, and extracted with EtOAc (2×400 mL). The combined extracts are washed with saturated brine, dried over sodium sulfate, filtered, and concentrated to a yellow solid (39 g, 97%). ESI/MS m/z 247.1 (M−H)−. cooled in an ice bath extracted with EtOAc (2×400 mL) The combined extracts are washed with saturated brine dried over sodium sulfate filtered concentrated to a yellow solid (39 g, 97%)

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

Procedure: To a 250 mL RB flask fitted with magnetic stirrer was charged 6 mL of dry THF under argon atmosphere. To the stirred solvent was added 5-(4-hydroxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (0.6 g, 2.41 mmol). The resulting mixture was cooled to 0° C. and was added cyclopropylmagnesium bromide (25 mL, 0.5 M in THF, 7.25 mmol). The resulting mixture was stirred at ambient temperatures for 2 h. Then, the reaction mass was quenched with 20 mL of 1N HCl then, ethyl acetate (50 mL) was added, stirred well and the layers were separated. The organic layer was washed with water (100 mL×3), brine solution. Then the organic layer was dried over anhydrous Na2SO4. The solvent was removed under reduced pressure, and the resulting crude compound is purified by column chromatography on silica gel (60-120 meshes) using petroleum ether (60-80) and ethyl acetate as eluent. The product was obtained as yellow solid. Yield: 42.76% (0.3 g) MS (ESI, 120 ev): m/z=291.1 (M+1). (300 MHz, DMSO-d6): δ 9.16 (s, 1H), 6.95-6.98 (d, 2H), 6.53-6.56 (d, 2H), 4.42-4.43 (d, 1H), 2.54-2.59 (m, 1H), 1.61 (s, 4H), 1.29 (s, 3H), 0.40-0.49 (m, 2H), 0.23-0.28 (m, 1H), 0.03-0.01 (m, 1H). To a 250 mL RB flask fitted with magnetic stirrer Then, the reaction mass was quenched with 20 mL of 1N HCl ethyl acetate (50 mL) was added stirred well the layers were separated The organic layer was washed with water (100 mL×3), brine solution Then the organic layer was dried over anhydrous Na2SO4 The solvent was removed under reduced pressure the resulting crude compound is purified by column chromatography on silica gel (60-120 meshes) The product was obtained as yellow solid

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

Procedure: To a 250 mL RB flask fitted with magnetic stirrer was charged 6 mL of dry THF under argon atmosphere. To the stirred solvent was added 5-(4-hydroxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (0.6 g, 2.41 mmol). The resulting mixture was cooled to 0° C. and was added cyclopropylmagnesium bromide (25 mL, 0.5 M in THF, 7.25 mmol). The resulting mixture was stirred at ambient temperatures for 2 h. Then, the reaction mass was quenched with 20 mL of 1N HCl then, ethyl acetate (50 mL) was added, stirred well and the layers were separated. The organic layer was washed with water (100 mL×3), brine solution. Then the organic layer was dried over anhydrous Na2SO4. The solvent was removed under reduced pressure, and the resulting crude compound is purified by column chromatography on silica gel (60-120 meshes) using petroleum ether (60-80) and ethyl acetate as eluent. The product was obtained as yellow solid. Yield: 42.76% (0.3 g) MS (ESI, 120 ev): m/z=291.1 (M+1). (300 MHz, DMSO-d6): δ 9.16 (s, 1H), 6.95-6.98 (d, 2H), 6.53-6.56 (d, 2H), 4.42-4.43 (d, 1H), 2.54-2.59 (m, 1H), 1.61 (s, 4H), 1.29 (s, 3H), 0.40-0.49 (m, 2H), 0.23-0.28 (m, 1H), 0.03-0.01 (m, 1H). To a 250 mL RB flask fitted with magnetic stirrer Then, the reaction mass was quenched with 20 mL of 1N HCl ethyl acetate (50 mL) was added stirred well the layers were separated The organic layer was washed with water (100 mL×3), brine solution Then the organic layer was dried over anhydrous Na2SO4 The solvent was removed under reduced pressure the resulting crude compound is purified by column chromatography on silica gel (60-120 meshes) The product was obtained as yellow solid

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

Procedure: To a 250 mL 3-necked RB flask fitted with magnetic stirrer was charged with bromo(prop-1-yn-1-yl)magnesium (42.5 mL, 211 mmol) in THF (30 mL). To the RM was added slowly 5-(4-hydroxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (5.0 g, 100.8 mmol) in THF (20 mL) under nitrogen atmosphere. The RM was stirred at room temperature about 30 minutes. The reaction mixture was diluted with NH4Cl solution and hexane. The aqueous layer was acidified with KHSO4 solution to adjust the pH 2 and extracted with ethyl acetate, washed with water, then dried to obtain the product (5.8 g, yield: 100.0%). To a 250 mL 3-necked RB flask fitted with magnetic stirrer extracted with ethyl acetate washed with water dried

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

Procedure: To a 250 mL 3-necked RB flask fitted with magnetic stirrer was charged with bromo(prop-1-yn-1-yl)magnesium (42.5 mL, 211 mmol) in THF (30 mL). To the RM was added slowly 5-(4-hydroxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (5.0 g, 100.8 mmol) in THF (20 mL) under nitrogen atmosphere. The RM was stirred at room temperature about 30 minutes. The reaction mixture was diluted with NH4Cl solution and hexane. The aqueous layer was acidified with KHSO4 solution to adjust the pH 2 and extracted with ethyl acetate, washed with water, then dried to obtain the product (5.8 g, yield: 100.0%). To a 250 mL 3-necked RB flask fitted with magnetic stirrer extracted with ethyl acetate washed with water dried

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 500 mL RB flask fitted with magnetic stirrer was charged with water (160 mL). To the stirred solvent was added 4-hydroxybenzaldehyde (25.0 g, 122.12 mmol) and 2,2-dimethyl-1,3-dioxane-4,6-dione (25.0 g), it was heated at 75° C. for 2 h. The RM was cooled to obtain the solid, filtered and was washed with water, then dried to obtain the product (34.0, yield: 83.74%). To a 500 mL RB flask fitted with magnetic stirrer The RM was cooled to obtain the solid filtered was washed with water dried to obtain the product (34.0, yield: 83.74%)

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

Procedure: Condensation with Meldrum's acid was carried out according to the method of Bigi et. al. (2001) Tetrahedron Lett. 42:5203-5205. A 2 L pear-shaped flask was charged with 4-hydroxybenzaldehyde (50 g, 409 mmol) and water (400 mL). The flask was placed in a water bath at 75° C., and Meldrum's acid (62 g, 430 mmol) was added as a slurry in 400 mL of water. The reaction mixture was agitated for 2 hours and cooled in an ice bath for 2 hours. The product was collected by filtration and rinsed with cold water. After drying thoroughly, adduct M1.1 was obtained as a fine yellow powder. MS ESI (pos.) m/e: 519.0 (2M+Na). 1H NMR (500 MHz) (DMSO-d6) δ 9.75 (br s, 1H); 8.27 (s, 1H); 8.24 (d, 2H, J=10 Hz); 6.98 (d, 2H, J=10 Hz);.1.76 (s, 6H). The flask was placed in a water bath at 75° C. cooled in an ice bath for 2 hours The product was collected by filtration rinsed with cold water After drying thoroughly adduct M1.1 was obtained as a fine yellow powder

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-propynyl magnesium bromide in THF (0.5 N, 322 mL, 161.28 mmol) is added a solution of 5-(4-hydroxy-benzylidene)-2,2-dimethyl-[1,3]dioxane-4,6-dione (20 g, 80.64 mmol) in THF (200 mL) by cannula under a nitrogen atmosphere. Over the course of the addition, the reaction mixture changed to a thick, yellow suspension. After addition is compete, the reaction mixture is stirred for 15 minutes at 50° C., quenched with aqueous NH4Cl, and acidified to pH ˜2 with 2 N HCl. The mixture is extracted with EtOAc (2×300 mL) and the combined extracts are washed with saturated brine, dried over MgSO4, filtered, and concentrated to a yellow solid (20 g, 86%). The product is carried on crude. Over the course of the addition After addition quenched with aqueous NH4Cl The mixture is extracted with EtOAc (2×300 mL) the combined extracts are washed with saturated brine dried over MgSO4 filtered concentrated to a yellow solid (20 g, 86%)