(2-methylphenyl)-phenylmethanone

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (4-Methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (300 mg, 1.4 mmol) is dissolved in dry THF (15 mL) and it is cooled down to −78° C. After 1.6 M n-BuLi (4.5 mL, 7.2 mmol) is added at −78° C., the cooling bath is removed and the mixture is stirred at room temperature for 15 min. Then the reaction mixture is cooled down to −78° C. again and phenyl-o-tolyl-methanone (1.3 mL, 7.2 mmol) is added. After the mixture is stirred for 30 min at −78° C., saturated NH4Cl aqueous solution (15 mL) is added and the reaction is warmed up to room temperature. EtOAc (60 mL) is added along with water (50 mL). The mixture is stirred for another 10 min and the aqueous layer is separated, extracted with EtOAc (2×35 ml). The organic layers are combined and concentrated to give the crude product. Purification by silica flash column chromatography using MeOH in DCM (gradient from 0% to 10%) affords 361 mg of the desired product. the cooling bath is removed Then the reaction mixture is cooled down to −78° C. again After the mixture is stirred for 30 min at −78° C. the reaction is warmed up to room temperature The mixture is stirred for another 10 min the aqueous layer is separated extracted with EtOAc (2×35 ml) concentrated to give the crude product Purification by silica flash column chromatography

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

Procedure: Methylbenzophenone was prepared from mixtures of toluene and benzoyl chloride using essentially the method described in Example 1, with the following modifications in the distillation scheme. described in Example 1, with the following modifications in the distillation scheme

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

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

Procedure: To a mixture of 2-methylbenzophenone (2.0 g, 10.2 mmol) and N-boc-3-pyrrolidone (1.89 g, 10.2 mmol) in THF was added zinc powder (3.3 g, 59 mmol) at 10-15° C. and stirred for 15 min. To the reaction mixture was added TiCl4 (4.76 g, 25 mmol) and the contents were brought to 60° C. and stirred for 8 h. The reaction mixture was allowed to cool to room temperature, diluted HCl was added and extracted with EtOAc. The organic layer was washed with aqueous sodium potassium tartarate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the crude product which was washed with n-hexane to afford 1.8 g of (Z)-3-(phenyl(m-tolyl)methylene)pyrrolidine. were brought to 60° C. stirred for 8 h extracted with EtOAc The organic layer was washed with aqueous sodium potassium tartarate solution The organic layer was dried over anhydrous sodium sulfate concentrated under reduced pressure to afford the crude product which was washed with n-hexane

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

Procedure: To a mixture of 2-methylbenzophenone (2.0 g, 10.2 mmol) and N-boc-3-pyrrolidone (1.89 g, 10.2 mmol) in THF was added zinc powder (3.3 g, 59 mmol) at 10-15° C. and stirred for 15 min. To the reaction mixture was added TiCl4 (4.76 g, 25 mmol) and the contents were brought to 60° C. and stirred for 8 h. The reaction mixture was allowed to cool to room temperature, diluted HCl was added and extracted with EtOAc. The organic layer was washed with aqueous sodium potassium tartarate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to afford the crude product which was washed with n-hexane to afford 1.8 g of (Z)-3-(phenyl(m-tolyl)methylene)pyrrolidine. were brought to 60° C. stirred for 8 h extracted with EtOAc The organic layer was washed with aqueous sodium potassium tartarate solution The organic layer was dried over anhydrous sodium sulfate concentrated under reduced pressure to afford the crude product which was washed with n-hexane

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

Procedure: Methylbenzophenone was prepared from mixtures of toluene and benzoyl chloride using essentially the method described in Example 1, with the following modifications in the distillation scheme. described in Example 1, with the following modifications in the distillation scheme

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

Procedure: Methylbenzophenone was prepared from mixtures of toluene and benzoyl chloride using essentially the method described in Example 1, with the following modifications in the distillation scheme. described in Example 1, with the following modifications in the distillation scheme

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

Procedure: The amount of 912 grams (4.65 moles) of methyl benzophenone was then melted and heated to 100°-110° C. in a two-liter, two-necked, round bottom flask with magnetic stirring. Chlorine gas was introduced through a gas dispersion tube immersed below the liquid at a rate such that the characteristic greenish color of chlorine was not detectable in the exiting stream of hydrogen chloride. Initially the reaction was exothermic and no additional external heating was required. After about seven hours the theoretical uptake in weight (160 g) had occured. The hot melt was poured into 6 liters of isopropyl alcohol. This mixture was chilled to -5° to 0° C. and the precipitated solid was removed by suction filtration to provide 618 grams (57% yield) of 4-(chloromethyl)benzophenone, mp 109°-111° C. A carbonyl band at 1670 cm-1 was noted in the infrared spectrum. heated to 100°-110° C. in a two-liter no additional external heating This mixture was chilled to -5° to 0° C. the precipitated solid was removed by suction filtration

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

Procedure: To a mechanically stirred solution of 1000 grams (7.12 moles) of benzoylchloride in 6000 grams of toluene was added 1000 grams (7.50 moles) of anhydrous aluminum chloride over a 20-30 minute period. The temperature of the reaction mixture rose to near the boiling point during the addition, and heating at reflux was maintained for three additional hours. After cooling, 1200 milliliters of water were added, slowly at first, followed by 1000 milliliters of concentrated hydrochloric acid. The organic layer was separated, washed twice with hot water and concentrated by simple distillation. Vacuum distillation of the residual oil provided 1300 grams (93% yield) of white, semi-solid methyl benzophenone; (b.p. 180°-200° C., 10-15 mm Hg; m.p. 50°-55° C.). The infrared spectrum revealed a carbonyl band at 1660 cm-1. The temperature of the reaction mixture rose to near the boiling point during the addition heating at reflux was maintained for three additional hours After cooling The organic layer was separated washed twice with hot water concentrated by simple distillation Vacuum distillation of the residual oil

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

Procedure: Potassium tert-butoxyde (8.64 g, 77 mmol) was added, in one portion, to a cold (0° C.) solution of Tosmic (6.04 g, 27.8 mmol) in DMSO (15 mL) and stirred for 5 min. MeOH (0.2 mL) was then added followed by phenyl(o-tolyl)methanone (1.82 g, 9.2 mmol) in one portion. The reaction was warmed up slowly over 12 hours to room temperature. The reaction mixture was partitioned between saturated aqueous sodium carbonate and ethyl acetate. The organic phase was dried over sodium sulfate and evaporated under reduced pressure to give a residue. TFA (3.85 mL, 50 mmol) in THF (5 mL) was slowly added to a cool (0° C.) suspension of sodium borohydride (2.1 g, 50 mmol) in THF (5 mL) over 10 minutes. To this solution was added the residue dissolved in THF (5 mL) over 5 minutes. The resulting mixture was warmed to room temperature and stirred 16 hrs. The reaction mixture was partitioned between saturated aqueous sodium carbonate and ethyl acetate. The organic phase was dried over sodium sulfate and evaporated under reduced pressure and dissolved in methanol. This solution was then passed through SCX resin (12 g, 0.78 mmol/g) and washed with methanol. These washes were discarded and the cartridge treated with 2M ammonia in methanol. The ammonia solution was then evaporated to generate the desired compound (1.322 g, 63%). 1H NMR (400 MHz, DMSO-d6) δ ppm: 2.22 (3H, s) 3.04-3.16 (2H, m) 4.13 (1H, t, J=7.45 Hz) 7.08-7.31 (11H, m). The reaction was warmed up slowly over 12 hours to room temperature The reaction mixture was partitioned between saturated aqueous sodium carbonate and ethyl acetate The organic phase was dried over sodium sulfate evaporated under reduced pressure to give a residue a cool To this solution was added the residue stirred 16 hrs The reaction mixture was partitioned between saturated aqueous sodium carbonate and ethyl acetate The organic phase was dried over sodium sulfate evaporated under reduced pressure dissolved in methanol washed with methanol the cartridge treated with 2M ammonia in methanol The ammonia solution was then evaporated

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

Procedure: To a mechanically stirred solution of 1000 grams (7.12 moles) of benzoyl chloride in 6000 grams of toluene was added 1000 grams (7.50 moles) of anhydrous aluminum chloride over a 20- 30 minute period. The temperature of the reaction mixture rose to near the boiling point during the addition, and heating at reflux was maintained for three additional hours. After cooling, 1200 milliliters of water were added, slowly at first, followed by 1000 milliliters of concentrated hydrochloric acid. The organic layer was separated, washed twice with hot water and concentrated on a rotary evaporator. Vacuum distillation of the residual oil provided 1300 grams (93% yield) of white, semi-solid methyl benzophenone; (b.p. 180°-200° C., 10- 15 mm Hg; m.p. 50° C.) The infrared spectrum revealed a carbonyl band at 1665 cm -1. The temperature of the reaction mixture rose to near the boiling point during the addition heating at reflux was maintained for three additional hours After cooling The organic layer was separated washed twice with hot water concentrated on a rotary evaporator Vacuum distillation of the residual oil