1-(4-hydroxyphenyl)propan-1-one

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:0.00; 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: p-Hydroxypropiophenone (50 g, 0.33 mmol) was reacted with 1-bromo-3-chloropropane and the resulting compound reacted with bromine as described in Example 1. The resulting compound was reacted with 3-methyl-2-aminopyridine (1.7 g, 16 mmol) and the product reacted with dibutylamine as described in Example 1 to produce 2.4 g (62% yield) of the title compound as the HCl salt, mp 202° C. to 204° C. IR(KBr): 3420, 2620, 1650, 1605 cm-1. MS: 408 (M+). 1H NMR (CD3OD): δ8.58 (d, J=6.5 Hz, 1H), 7.85-7.71 (m, 3H), 7.48 (t, J=6.7 Hz, 1H), 7.22 (d, J=8.7 Hz, 2H), 4.26 (t, J=5.8 Hz, 2H), 3.52-3.16 (m, 6H), 2.75 (s, 3H), 2.73 (s, 3H), 2.33 (m, 2H), 1.87-1.36 (m, 8H), 1.02 (m, 6H).

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

Procedure: To 10 ml of di-n-butyl ether were added 6.0 g of 4'-hydroxypropiophenone. 6.6 Grams of bromine were added dropwise to the mixture with stirring at room temperature, and the reaction liquid was stirred for an additional 10 minutes. To the reaction liquid were then added 7.5 g of 4-benzylpyridine, 4.0 g of potassium hydrogen carbonate, 1 ml of water and 50 ml of methanol, and the mixture was refluxed under heating for 5 hours. After stopping the heating, the reaction mixture was treated in the same manner as described in Example 46, whereby 11.7 g (76.0%) of ifenprodil were obtained as white crystals. the reaction liquid was stirred for an additional 10 minutes To the reaction liquid the mixture was refluxed under heating for 5 hours the reaction mixture was treated in the same manner

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

Procedure: To 4 ml of dioxane were added 6.0 g of 4'-hydroxypropiophenone. 6.8 Grams of bromine were added dropwise to the mixture with stirring at room temperature, and the reaction liquid was stirred for an additional 10 minutes. To the reaction liquid were then added 14.3 g of 4-benzylpyridine and 100 ml of methanol, and the mixture was refluxed under heating for 3 hours. After stopping the heating, 0.5 g of platinum oxide were added and hydrogen was then introduced and the mixture was stirred for 12 hours under pressure of about 1 atm. After completion of the reaction, the reaction mixture was worked up in the same manner as described in Example 45, whereby 12.0 g (74.1%) of ifenprodil hydrobromide were obtained as white crystals. the reaction liquid was stirred for an additional 10 minutes To the reaction liquid the mixture was refluxed under heating for 3 hours were added the mixture was stirred for 12 hours under pressure of about 1 atm After completion of the reaction

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

Procedure: To 4 ml of dioxane were added 6.0 g of 4'-hydroxypropiophenone. 6.8 Grams of bromine were added dropwise to the mixture with stirring at room temperature, and the reaction liquid was stirred for an additional 10 minutes. To the reaction liquid were then added 7.5 g of 4-benzylpyridine, 3.3 g of anhydrous sodium acetate and 100 ml of ethanol, and the mixture was refluxed under heating for 3 hours. After stopping the heating, 0.5 g of platinum oxide and 200 ml of ethanol were added and hydrogen was then introduced and the mixture was stirred for 9 hours under pressure of about 1 atm. After completion of the reaction, the reaction mixture was treated in the same manner as described in Example 46, whereby 10.9 g (70.8%) of ifenprodil were obtained as white crystals. the reaction liquid was stirred for an additional 10 minutes To the reaction liquid the mixture was refluxed under heating for 3 hours were added the mixture was stirred for 9 hours under pressure of about 1 atm After completion of the reaction the reaction mixture was treated in the same manner

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

Procedure: To 4 ml of dioxane were added 6.0 g of 4'-hydroxypropiophenone. 6.8 Grams of bromine were added dropwise to the mixture with stirring at room temperature, and the reaction liquid was stirred for an additional 5 minutes. To the reaction liquid were then added 8.1 g of 4-benzylpyridine, 100 ml of methanol and 3.3 g of anhydrous sodium acetate, and the mixture was refluxed under heating for 5 hours. After refluxing the mixture, the reaction mixture was worked up in the same manner as described in Example 46, whereby 12.3 g (79.9%) of ifenprodil were obtained as white crystals. the reaction liquid was stirred for an additional 5 minutes To the reaction liquid the mixture was refluxed under heating for 5 hours After refluxing the mixture

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

Procedure: To 4 ml of dioxane were added 6.0 g of 4'-hydroxypropiophenone. 6.8 Grams of bromine were added dropwise to the mixture with stirring at room temperature, and the reaction liquid was stirred for an additional 5 minutes. To the reaction liquid were then added 7.5 g of 4-benzylpyridine, 2.8 ml of 10-N sodium hydroxide solution and 100 ml of methanol, and the mixture was refluxed under heating for 5 hours. After stopping the heating, 0.5 g of platinum oxide were added and hydrogen was then introduced and the mixture was stirred for 7 hours under pressure of about 1 atm. After completion of the reaction, the reaction mixture was worked up in the same manner as described in Example 46, whereby 11.5 g (74.7%) of ifenprodil were obtained as white crystals. the reaction liquid was stirred for an additional 5 minutes To the reaction liquid the mixture was refluxed under heating for 5 hours were added the mixture was stirred for 7 hours under pressure of about 1 atm After completion of the reaction

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

Procedure: To 4 ml of dioxane were added 6.0 g of 4'-hydroxypropiophenone. 6.8 Grams of bromine were added dropwise to the mixture with stirring at room temperature, and the reaction liquid was stirred for an additional 10 minutes. To the reaction liquid were then added 7.5 g of 4-benzylpyridine, 2.1 g of potassium carbonate, 1 ml of water and 50 ml of methanol, and the mixture was refluxed under heating for 5 hours. After stopping the heating, 25 ml of methanol and 0.2 g of platinum oxide were added and hydrogen was then introduced and the mixture was stirred for 8 hours under pressure of about 1 atm. After completion of the reaction, the reaction mixture was worked up in the same manner as described in Example 46, whereby 12.0 g (77.9%) of ifenprodil were obtained as white crystals. the reaction liquid was stirred for an additional 10 minutes To the reaction liquid the mixture was refluxed under heating for 5 hours were added the mixture was stirred for 8 hours under pressure of about 1 atm After completion of the reaction