2-chloro-2,2-diphenylacetyl chloride

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

Procedure: A mixture of 15.5 g of diphenylchloroacetic acid morpholide, m.p. 113° C (prepared from diphenylchloroacetyl chloride and morpholine in accordance with the procedure described in Ber. 41, 3593) and 11g of imidazole in 100 ml of acetonitrile is heated at reflux for 18 hours. The solvent is removed by distillation in vacuo and, after addition of 70 ml of water, the residue is extracted with methylene chloride. The extracts are dried and the solvent is removed by distillation to yield diphenyl-imidazolylacetic acid morpholide which is further purified by recrystallization from methanol. The hydrochloride salt, m.p. 118° C, is obtained by treating an ethyl acetate solution of the free base with an ethereal solution of hydrogen chloride. at reflux for 18 hours The solvent is removed by distillation in vacuo after addition of 70 ml of water the residue is extracted with methylene chloride The extracts are dried the solvent is removed by distillation

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

Procedure: A mixture of chlorodiphenylacetyl chloride (20 g), 1-methyl-3-pyrrolidinol (7.6 g), and pyridine (35 g) is kept at room temperature for two hours. After adding 45 g of 2-benzyloxyethanol, the mixture is refluxed gently for 18 hours. Excess pyridine and benzyloxyethanol are distilled off under reduced pressure, the residue is dissolved in ether and washed twice with water. The organic phase is dried over magnesium sulfate (MgSO4), filtered and the filtrate evaporated to dryness. Chromatography of the residue on the silica gel with ethyl acetate-hexane-triethylamine (50:50:1) as eluent affords 18 g of 1-methyl-3-[2,2-diphenyl-2-(2-benzyloxyethoxy)acetoxy]pyrrolidine as an oil. the mixture is refluxed gently for 18 hours Excess pyridine and benzyloxyethanol are distilled off under reduced pressure the residue is dissolved in ether washed twice with water The organic phase is dried over magnesium sulfate (MgSO4) filtered the filtrate evaporated to dryness

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

Procedure: A mixture of 15.5 g of diphenylchloroacetic acid morpholide, m.p. 113° C (prepared from diphenylchloroacetyl chloride and morpholine in accordance with the procedure described in Ber. 41, 3593) and 11g of imidazole in 100 ml of acetonitrile is heated at reflux for 18 hours. The solvent is removed by distillation in vacuo and, after addition of 70 ml of water, the residue is extracted with methylene chloride. The extracts are dried and the solvent is removed by distillation to yield diphenyl-imidazolylacetic acid morpholide which is further purified by recrystallization from methanol. The hydrochloride salt, m.p. 118° C, is obtained by treating an ethyl acetate solution of the free base with an ethereal solution of hydrogen chloride. at reflux for 18 hours The solvent is removed by distillation in vacuo after addition of 70 ml of water the residue is extracted with methylene chloride The extracts are dried the solvent is removed by distillation

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

Procedure: A mixture of 15.5 g of diphenylchloroacetic acid morpholide, m.p. 113° C (prepared from diphenylchloroacetyl chloride and morpholine in accordance with the procedure described in Ber. 41, 3593) and 11g of imidazole in 100 ml of acetonitrile is heated at reflux for 18 hours. The solvent is removed by distillation in vacuo and, after addition of 70 ml of water, the residue is extracted with methylene chloride. The extracts are dried and the solvent is removed by distillation to yield diphenyl-imidazolylacetic acid morpholide which is further purified by recrystallization from methanol. The hydrochloride salt, m.p. 118° C, is obtained by treating an ethyl acetate solution of the free base with an ethereal solution of hydrogen chloride. at reflux for 18 hours The solvent is removed by distillation in vacuo after addition of 70 ml of water the residue is extracted with methylene chloride The extracts are dried the solvent is removed by distillation

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

Procedure: 10 g (38 mmole) of 2-chloro-2,2-diphenylacetyl chloride were slowly added to a chilled solution of 7.6 ml 5M sodium hydroxide (38 mmole) and 5.3 g (38 mmole) of diisopropylaminoethylamine in 50 ml of methylene chloride. The temperature was kept at 0° C. with good agitation. The mixture was stirred for 1 h. The water solution was discarded and the organic layer was washed with water and dried over anhydrous sodium sulfate. The solution was evaporated to dryness and the remaining oil solidified. The product was dissolved in 2M hydrochloric acid and heated for 10 min on a steambath to hydrolyze the 2-chloro to a hydroxyl group. The solution was chilled to room temperature and was extracted with methylene chloride. The methylene chloride solution was evaporated and the product was crystallised from warm acetone. was kept at 0° C. with good agitation the organic layer was washed with water dried over anhydrous sodium sulfate The solution was evaporated to dryness The product was dissolved in 2M hydrochloric acid heated for 10 min on a steambath was extracted with methylene chloride The methylene chloride solution was evaporated the product was crystallised from warm acetone

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

Procedure: An acetone solution of 1 mol of diphenyl-α-chloroacetyl chloride is treated at 0° C. with an acetone solution of pyrrolidinoethylamine.

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

Procedure: A mixture of chlorodiphenylacetyl chloride (20 g), 1-methyl-3-pyrrolidinol (7.6 g), and pyridine (35 g) is kept at room temperature for two hours. After adding 45 g of 2-benzyloxyethanol, the mixture is refluxed gently for 18 hours. Excess pyridine and benzyloxyethanol are distilled off under reduced pressure, the residue is dissolved in ether and washed twice with water. The organic phase is dried over magnesium sulfate (MgSO4), filtered and the filtrate evaporated to dryness. Chromatography of the residue on the silica gel with ethyl acetate-hexane-triethylamine (50:50:1) as eluent affords 18 g of 1-methyl-3-[2,2-diphenyl-2-(2-benzyloxyethoxy)acetoxy]pyrrolidine as an oil. the mixture is refluxed gently for 18 hours Excess pyridine and benzyloxyethanol are distilled off under reduced pressure the residue is dissolved in ether washed twice with water The organic phase is dried over magnesium sulfate (MgSO4) filtered the filtrate evaporated to dryness

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

Procedure: A mixture of 15.5 g of diphenylchloroacetic acid morpholide, m.p. 113° C (prepared from diphenylchloroacetyl chloride and morpholine in accordance with the procedure described in Ber. 41, 3593) and 11g of imidazole in 100 ml of acetonitrile is heated at reflux for 18 hours. The solvent is removed by distillation in vacuo and, after addition of 70 ml of water, the residue is extracted with methylene chloride. The extracts are dried and the solvent is removed by distillation to yield diphenyl-imidazolylacetic acid morpholide which is further purified by recrystallization from methanol. The hydrochloride salt, m.p. 118° C, is obtained by treating an ethyl acetate solution of the free base with an ethereal solution of hydrogen chloride. at reflux for 18 hours The solvent is removed by distillation in vacuo after addition of 70 ml of water the residue is extracted with methylene chloride The extracts are dried the solvent is removed by distillation