2-hydroxy-6-(methoxymethoxy)benzaldehyde

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 2-hydroxy-6-methoxymethoxybenzaldehyde (0.91 g, 5.1 mM) in dry dimethyl sulphoxide (8 ml) was added potassium t-butoxide (0.57 g, 5.1 mM) with exclusion of moisture. After 10 mins, ethyl 4-bromomethylbenzoate (1.22 g, 5 mM) was added and the whole stirred at room temperature (18 hrs). The reaction mixture was poured into water (100 ml) and the liberated oil extracted into ether. The combined extracts were washed with 5% sodium carbonate solution, water, dried (sodium sulphate) and evaporated. The residual oil (ethyl 4-(2-formyl-3-methoxymethoxyphenoxymethyl)benzoate was dissolved in ethanol (30 ml) and treated with 3 M hydrochloric acid (30 ml) with stirring at 60° C. (30 mins). The solid was filtered off, washed with water, dried, and recrystallised from ethanol/water to give ethyl 4-(2-formyl-3-hydroxyphenoxymethyl)benzoate, m.p. 105°-ω° C. (identical to a sample previously prepared, Example 5(B)). the liberated oil extracted into ether The combined extracts were washed with 5% sodium carbonate solution, water dried (sodium sulphate) evaporated The residual oil (ethyl 4-(2-formyl-3-methoxymethoxyphenoxymethyl)benzoate was dissolved in ethanol (30 ml) treated with 3 M hydrochloric acid (30 ml) with stirring at 60° C. (30 mins) The solid was filtered off washed with water dried recrystallised from ethanol/water

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

Procedure: To a stirred solution of 2-hydroxy-6-methoxymethoxybenzaldehyde (0.91 g, 5.1 mM) in dry dimethyl sulphoxide (8 ml) was added potassium t-butoxide (0.57 g, 5.1 mM) with exclusion of moisture. After 10 mins, ethyl 4-bromomethylbenzoate (1.22 g, 5 mM) was added and the whole stirred at room temperature (18 hrs). The reaction mixture was poured into water (100 ml) and the liberated oil extracted into ether. The combined extracts were washed with 5% sodium carbonate solution, water, dried (sodium sulphate) and evaporated. The residual oil (ethyl 4-(2-formyl-3-methoxymethoxyphenoxymethyl)benzoate was dissolved in ethanol (30 ml) and treated with 3 M hydrochloric acid (30 ml) with stirring at 60° C. (30 mins). The solid was filtered off, washed with water, dried, and recrystallised from ethanol/water to give ethyl 4-(2-formyl-3-hydroxyphenoxymethyl)benzoate, m.p. 105°-ω° C. (identical to a sample previously prepared, Example 5(B)). the liberated oil extracted into ether The combined extracts were washed with 5% sodium carbonate solution, water dried (sodium sulphate) evaporated The residual oil (ethyl 4-(2-formyl-3-methoxymethoxyphenoxymethyl)benzoate was dissolved in ethanol (30 ml) treated with 3 M hydrochloric acid (30 ml) with stirring at 60° C. (30 mins) The solid was filtered off washed with water dried recrystallised from ethanol/water

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloro-N-(1-ethyl-1H-pyrazol-5-yl)-N-isopropylacetamide (0.39 g, 1.7 mmol) and 2-hydroxy-6-(methoxymethoxy)benzaldehyde (0.309 g, 1.7 mmol) were dissolved in DMF (8.5 ml) and purged with N2 gas. Potassium carbonate (0.47 g, 3.4 mmol) was added and the mixture was stirred in a heat block at 60° C. After 2 h, the reaction was cooled and partitioned into ethyl acetate (100 ml) and water (100 ml). The phases were separated and the aqueous phase was extracted with ethyl acetate (2×50 ml). The combined organic phases were washed with water (50 ml) and a saturated aqueous sodium chloride solution (50 ml), and dried over sodium sulfate. After evaporation the residue was purified by silica gel chromatography (5-50% ethyl acetate/hexanes) to give 0.38 g (59%) of N-(1-ethyl-1H-pyrazol-5-yl)-2-(2-formyl-3-(methoxymethoxy)phenoxy)-N-isopropylacetamide as a faintly-colored viscous oil. MS (ESI) m/z 376 [M+H]+. purged with N2 gas the reaction was cooled partitioned into ethyl acetate (100 ml) and water (100 ml) The phases were separated the aqueous phase was extracted with ethyl acetate (2×50 ml) The combined organic phases were washed with water (50 ml) a saturated aqueous sodium chloride solution (50 ml), and dried over sodium sulfate After evaporation the residue was purified by silica gel chromatography (5-50% ethyl acetate/hexanes)

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

Procedure: To a stirred solution of 2-hydroxy-6-methoxymethoxybenzaldehyde (0.91 g, 5.1 mM) in dry dimethyl sulphoxide (8 ml) was added potassium t-butoxide (0.57 g, 5.1 mM) with exclusion of moisture. After 10 mins, ethyl 4-bromomethylbenzoate (1.22 g, 5 mM) was added and the whole stirred at room temperature (18 hrs). The reaction mixture was poured into water (100 ml) and the liberated oil extracted into ether. The combined extracts were washed with 5% sodium carbonate solution, water, dried (sodium sulphate) and evaporated. The residual oil (ethyl 4-(2-formyl-3-methoxymethoxyphenoxymethyl)benzoate was dissolved in ethanol (30 ml) and treated with 3 M hydrochloric acid (30 ml) with stirring at 60° C. (30 mins). The solid was filtered off, washed with water, dried, and recrystallised from ethanol/water to give ethyl 4-(2-formyl-3-hydroxyphenoxymethyl)benzoate, m.p. 105°-ω° C. (identical to a sample previously prepared, Example 5(B)). the liberated oil extracted into ether The combined extracts were washed with 5% sodium carbonate solution, water dried (sodium sulphate) evaporated The residual oil (ethyl 4-(2-formyl-3-methoxymethoxyphenoxymethyl)benzoate was dissolved in ethanol (30 ml) treated with 3 M hydrochloric acid (30 ml) with stirring at 60° C. (30 mins) The solid was filtered off washed with water dried recrystallised from ethanol/water