3-ethoxy-2-hydroxybenzaldehyde

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

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

Procedure: 23.3 g of ω-bromo-p-chloroacetophenone are added to 17 g of 3-ethoxysalicylaldehyde in 800 ml of ethanol and 4 g of sodium hydrate. After heating the mixture for one hour under reflux, it is allowed to cool, the product which separates is filtered off, and is crystallised from ethanol: M.P. 108°-110° C. After heating the mixture for one hour under reflux to cool the product which separates is filtered off is crystallised from ethanol

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

Procedure: A solution of 3-ethoxysalicylaldehyde (1 mmol) and 4-methoxyanilinosulfonyl acetic acid (1 mmol) in acetic acid (10 mL) was subjected to the General Procedure 1, Method A to yield the title compound; m.p. 206-209° C.

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

Procedure: A solution of 3-ethoxysalicylaldehyde (1 mmol) and 3-amino-4-fluoroanilinosulfonyl acetic acid (1 mmol) in acetic acid (10 mL) was subjected to the General Procedure 1, Method A to yield the title compound; m.p. 160-162° C.

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

Procedure: A solution of 3-ethoxysalicylaldehyde (1 mmol) and 4-methoxyanilinosulfonyl acetic acid (1 mmol) in acetic acid (10 mL) was subjected to the General Procedure 1, Method A to yield the title compound; m.p. 196-198° C.

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

Procedure: Bromine (2.95 g, 15.95 mmol) was added to a stirring solution of 3-ethoxy-2-hydroxybenzaldehyde (5.30 g, 31.9 mmol), which was dissolved in 30% HBr/HOAc The solution was stirred for 1.5 hrs at r.t. The reaction was quenched with H2O and extracted with ethyl acetate. The organic layer was washed with sat. ammonium chloride and dried over anhydrous sodium sulfate. Upon filtration the filtrate was concentrated in vacuo and purified by flash chromatography (silica gel) and eluted with 5% EtOAc/hexanes to yield 1.56 g (20%) of the title compound as a colorless oil: ESHRMS m/z 242.9657 (M−H, C9H9O3Br, Calc'd 242.9662). The reaction was quenched with H2O extracted with ethyl acetate The organic layer was washed with sat. ammonium chloride dried over anhydrous sodium sulfate Upon filtration the filtrate was concentrated in vacuo purified by flash chromatography (silica gel) eluted with 5% EtOAc/hexanes

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

Procedure: Bromine (2.95 g, 15.95 mmol) was added to a stirring solution of 3-ethoxy-2-hydroxybenzaldehyde (5.30 g, 31.9 mmol), which was dissolved in 30% HBr/HOAc The solution was stirred for 1.5 hrs at r.t. The reaction was quenched with H2O and extracted with ethyl acetate. The organic layer was washed with sat. ammonium chloride and dried over anhydrous sodium sulfate. Upon filtration the filtrate was concentrated in vacuo and purified by flash chromatography (silica gel) and eluted with 5% EtOAc/hexanes to yield 1.56 g (20%) of the title compound as a colorless oil: ESHRMS m/z 242.9657 (M−H, C9H9O3Br, Calc'd 242.9662). The reaction was quenched with H2O extracted with ethyl acetate The organic layer was washed with sat. ammonium chloride dried over anhydrous sodium sulfate Upon filtration the filtrate was concentrated in vacuo purified by flash chromatography (silica gel) eluted with 5% EtOAc/hexanes

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

Procedure: 3-Ethoxysalicylaldehyde (498 g, 3 moles) and sodium hydroxide (140 g, 3.5 moles) in 1.5 liters of water are introduced into a 4 liter reactor provided with mechanical stirring, a condenser and a nitrogen inlet. The mixture is taken to 60° C. and benzenesulphonyl chloride is added dropwise over three-quarters of an hour. The mixture is heated to 75° C. for a quarter of an hour. It is cooled. An oil forms which crystallizes with time. It is filtered, washed with water and dried. The 2-hydroxy-3-ethoxybenzaldehyde benzenesulphonate (901 g, yield=98%) is used for the following stage. It can be recrystallized from 90:10 acetic acid/water. A white powder is obtained, m.p.=68°-69° C. provided with mechanical stirring, a condenser and a nitrogen inlet is taken to 60° C. It is cooled An oil forms which crystallizes with time It is filtered washed with water dried

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

Procedure: 23.3 g of ω-bromo-p-chloroacetophenone are added to 17 g of 3-ethoxysalicylaldehyde in 800 ml of ethanol and 4 g of sodium hydrate. After heating the mixture for one hour under reflux, it is allowed to cool, the product which separates is filtered off, and is crystallised from ethanol: M.P. 108°-110° C. After heating the mixture for one hour under reflux to cool the product which separates is filtered off is crystallised from ethanol

Conditions: temp:22.01; pressure:0.00; stir:

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

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

Procedure: The title compound was prepared from {3-[3-benzyl-8-(trifluoromethyl)quinolin-4-yl]phenyl}amine and 3-ethoxy-2-hydroxybenzaldehyde according to the procedure of step 1, Example 66. MS (ESI) m/z 529; MS (ESI) m/z 527.