1-hydroxypropan-2-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:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 17 mL 2 mol/L aqueous sodium hydroxide solution was dropped to 6.7 g 4-cyano-piperazine-1-carboxylic acid tert-butyl ester and 2.5 mL 1-hydroxy-propan-2-one in 10 mL THF. The reaction was stirred 12 h at RT and over night at 75° C. The reaction was cooled, water was added and the mixture was diluted with diethylether. The precipitate was filtered to give 1.32 g of the desired product. The reaction was cooled The precipitate was filtered

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

Procedure: A solution of 2-(3,4-difluorophenyl)-4-hydroxy-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (378 mg, 1 mmol), Ph3P (524 mg, 2 mmol) and acetol (74 mg, 1 mmol) in THF (25 mL) at room temperature was treated dropwise with a solution of DIAD (0.4 mL, 2 mmol) in THF (5 mL). The mixture was stirred at room temperature for 6 hours and concentrated in vacuo. The residue was chromatographed (silica gel, 1:1 hexanes-ethyl acetate) to provide the desired product (yield: 205 mg, 48%). mp 169-170° C.; 1H NMR (300 MHz, DMSO-d6) δ 2.08 (s, 3H), 3.30 (s, 3H), 5.30 (s, 2H), 7.48 (m, 1H), 7.62 (q, J=10 Hz, 1H), 7.75 (m, 1H), 7.94 (d, J=9 Hz, 2H), 8.05 (d, J=9 Hz, 2H), 8.21 (s, 1H); MS (APCI+) m/z 435 (M+H)+, (APCI−) m/z 469 (M+Cl)-; Anal. calc. for C20H16F2N2O5S.0.75H2O: C, 53.62; H, 3.93; N, 6.25. Found: C, 53.26; H, 3.61; N, 6.08. concentrated in vacuo The residue was chromatographed (silica gel, 1:1 hexanes-ethyl acetate)

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

Procedure: 2,3,4-trifluoroaniline was reductively alkylated in the presence hydroxyacetone using a Raney Nickel catalyst. Raney nickel (14 ml of 50% aqueous Raney nickel catalyst was slurried in 100 ml of absolute methanol. The mixture was allowed to settle and 90-95% of the liquid was decanted. The process was then repeated three times. 2,3,4-Trifluoroaniline (7.3 g, 0.05 mole) was charged into a glass autoclave liner containing the catalyst. Hydroxyacetone (3.7 g, 0.05 mole) was then added and the mixture was purged with nitrogen. Hydrogenation was initiated at 65° C. and continued to a maximum temperature of 85° C. Hydrogen uptake continued for 0.5 hour between 430 and 450 psi at which time 75% of the alkylated product (3) was obtained with the remainder being unreacted 2,3,4-trifluoroaniline and hydroxyacetone.

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

Procedure: 2,3,4-trifluoroaniline was reductively alkylated in the presence hydroxyacetone using a Raney Nickel catalyst. Raney nickel (14 ml of 50% aqueous Raney nickel catalyst was slurried in 100 ml of absolute methanol. The mixture was allowed to settle and 90-95% of the liquid was decanted. The process was then repeated three times. 2,3,4-Trifluoroaniline (7.3 g, 0.05 mole) was charged into a glass autoclave liner containing the catalyst. Hydroxyacetone (3.7 g, 0.05 mole) was then added and the mixture was purged with nitrogen. Hydrogenation was initiated at 65° C. and continued to a maximum temperature of 85° C. Hydrogen uptake continued for 0.5 hour between 430 and 450 psi at which time 75% of the alkylated product (3) was obtained with the remainder being unreacted 2,3,4-trifluoroaniline and hydroxyacetone.

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

Procedure: 2,3,4-trifluoroaniline was reductively alkylated in the presence of hydroxyacetone using a sulfided palladium on carbon catalyst. 30 g of 5% Pd/C catalyst (50% H2O)) was slurried in 200 ml of absolute methanol. The mixture was allowed to settle and 90-95% of the liquid was decanted. This process was repeated three times. 2,3,4-Trifluoroaniline (118 g, 0.8 mole) was charged into a glass autoclave liner containing the catalyst. Hydroxyacetone (80 g, 1.08 mole) was then added and the mixture was purged with nitrogen. Hydrogenation was initiated at 65° C. and continued to a maximum temperature of 107° C. Hydrogen uptake continued for one hour between 430 and 450 psi at which time 75% of the alkylated product (3) was obtained with the remainder being unreacted 2,3,4-trifluoroaniline and hydroxyacetone.

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

Procedure: 2,3,4-trifluoroaniline was reductively alkylated in the presence of hydroxyacetone using a sulfided palladium on carbon catalyst. 30 g of 5% Pd/C catalyst (50% H2O)) was slurried in 200 ml of absolute methanol. The mixture was allowed to settle and 90-95% of the liquid was decanted. This process was repeated three times. 2,3,4-Trifluoroaniline (118 g, 0.8 mole) was charged into a glass autoclave liner containing the catalyst. Hydroxyacetone (80 g, 1.08 mole) was then added and the mixture was purged with nitrogen. Hydrogenation was initiated at 65° C. and continued to a maximum temperature of 107° C. Hydrogen uptake continued for one hour between 430 and 450 psi at which time 75% of the alkylated product (3) was obtained with the remainder being unreacted 2,3,4-trifluoroaniline and hydroxyacetone.

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

Procedure: 2,3,4-Trifluoroaniline was reductively alkylated in the presence of hydroxyacetone using a palladium on carbon catalyst. 30 g of a 5% Pd/C catalyst (57.3% H2O)) was slurried in 200 ml of absolute methanol. The mixture was allowed to settle and 90-95% of the liquid was decanted. The process was then repeated three times. 2,3,4-trifluoroaniline (118 g, 0.8 mole) of was charged into a glass autoclave liner containing the catalyst. Hydroxyacetone (80 g, 1.08 mole) was then added and the mixture was purged with nitrogen. Hydrogenation was initiated at 65° C. and continued to a maximum temperature of 107° C. Hydrogen uptake continued for one hour at a pressure of between 430 and 450 psi at which time 75% of the alkylated product (3) was obtained with the remainder being unreacted 2,3,4-trifluoroaniline and hydroxyacetone. 90-95% of the liquid was decanted containing the catalyst the mixture was purged with nitrogen was initiated at 65° C. continued to a maximum temperature of 107° C was obtained with the remainder

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

Procedure: 2,3,4-Trifluoroaniline was reductively alkylated in the presence of hydroxyacetone using a palladium on carbon catalyst. 30 g of a 5% Pd/C catalyst (57.3% H2O)) was slurried in 200 ml of absolute methanol. The mixture was allowed to settle and 90-95% of the liquid was decanted. The process was then repeated three times. 2,3,4-trifluoroaniline (118 g, 0.8 mole) of was charged into a glass autoclave liner containing the catalyst. Hydroxyacetone (80 g, 1.08 mole) was then added and the mixture was purged with nitrogen. Hydrogenation was initiated at 65° C. and continued to a maximum temperature of 107° C. Hydrogen uptake continued for one hour at a pressure of between 430 and 450 psi at which time 75% of the alkylated product (3) was obtained with the remainder being unreacted 2,3,4-trifluoroaniline and hydroxyacetone. 90-95% of the liquid was decanted containing the catalyst the mixture was purged with nitrogen was initiated at 65° C. continued to a maximum temperature of 107° C was obtained with the remainder