2-chloro-2-fluoroacetyl chloride

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: Prepared as described in Example 1 using (1S,2R)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-phenylpropan-2-amine (1a, 18 mg, 50 μmol) and chlorofluoroacetyl chloride (19 mg, 150 μmol). Yield 16 mg (70%). Prepared

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

Procedure: NH3 is passed into a solution of 3.26 g. of 2-(α-chloro-α-fluoro-acetamido)-5-chloro-benzophenone, obtainable from 2-amino-5-chlorobenzophenone and α-chloro-α-fluoroacetyl chloride, in 15 ml. of DMSO at 50° for one hour. After stirring for 16 hours, the mixture is evaporated; 35 ml. of chloroform and 35 ml. of 13% NHO3 are added and the resulting salt is filtered off. The product is suspended in ethanol and neutralized with ammonia. Dilution with water gives 3-fluoro-5-phenyl-7-chloro-2,3-dihydro-1H-1,4-benzodiazepin-2-one, m.p. 235° (decomposition). the mixture is evaporated of 13% NHO3 are added the resulting salt is filtered off

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 4-amino-thiophene-3-carboxylic acid methyl ester (2 g) in dichloromethane (25 mL) was added chlorofluoroacetyl chloride (1.16 mL) and the reaction mixture was stirred to −15° C. Then a solution of triethylamine (3.2 mL) in dichloromethane (5 mL) was added slowly to the cold reaction mixture which was then allowed to warm up and stirred at room temperature for one hour. The reaction mixture was then diluted with further methylene chloride and washed several times with water, dried with sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography to yield the title compound as a light yellow solid. MS (EI): 251.1; mp=51-54° C. to warm up stirred at room temperature for one hour washed several times with water dried with sodium sulfate concentrated in vacuo The residue was purified by column chromatography

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

Procedure: Prepared as described in Example 1 using (1S,2R)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-phenylpropan-2-amine (1a, 18 mg, 50 μmol) and chlorofluoroacetyl chloride (19 mg, 150 μmol). Yield 16 mg (70%). Prepared

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

Procedure: NH3 is passed into a solution of 3.26 g. of 2-(α-chloro-α-fluoro-acetamido)-5-chloro-benzophenone, obtainable from 2-amino-5-chlorobenzophenone and α-chloro-α-fluoroacetyl chloride, in 15 ml. of DMSO at 50° for one hour. After stirring for 16 hours, the mixture is evaporated; 35 ml. of chloroform and 35 ml. of 13% NHO3 are added and the resulting salt is filtered off. The product is suspended in ethanol and neutralized with ammonia. Dilution with water gives 3-fluoro-5-phenyl-7-chloro-2,3-dihydro-1H-1,4-benzodiazepin-2-one, m.p. 235° (decomposition). the mixture is evaporated of 13% NHO3 are added the resulting salt is filtered off

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

Conditions: temp:-15.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a suspension of 4-amino-thiophene-3-carboxylic acid methyl ester (2 g) in dichloromethane (25 mL) was added chlorofluoroacetyl chloride (1.16 mL) and the reaction mixture was stirred to −15° C. Then a solution of triethylamine (3.2 mL) in dichloromethane (5 mL) was added slowly to the cold reaction mixture which was then allowed to warm up and stirred at room temperature for one hour. The reaction mixture was then diluted with further methylene chloride and washed several times with water, dried with sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography to yield the title compound as a light yellow solid. MS (EI): 251.1; mp=51-54° C. to warm up stirred at room temperature for one hour washed several times with water dried with sodium sulfate concentrated in vacuo The residue was purified by column chromatography

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

Procedure: Prepared as described in Example 1 using (1S,2R)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-phenylpropan-2-amine (1a, 18 mg, 50 μmol) and chlorofluoroacetyl chloride (19 mg, 150 μmol). Yield 16 mg (70%). Prepared

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

Procedure: Water, 250 ml, was added to a solution of 50 g (0.203 mole) of 2-amino-5-chlorobenzophenone oxime (mixture of isomers) in 1 l. of ether, and the mixture was stirred rapidly and cooled to 5°. Solutions of (A) 100 ml of 10% sodium hydroxide in water and (B) 33.5 g (0.228 mole) of chlorofluoroacetyl chloride made up to 100 ml with ether were simultaneously added at the same rate over 30 min., keeping the temperature of the reaction mixture at about 10° with cooling. The reaction mixture was stirred for 30 min. after the addition, and the ether layer was separated, washed with water, dried (MgSO4), and evaporated to dryness under reduced pressure. The residue was recrystallized from benzene to give 61.2 g (88%) of 2-(chlorofluoroacetamido)-5-chlorobenzophenone oxime (mixture of isomers) as light yellow crystals, mp 110°-129°. The 19F nmr (acetone-d6) indicates a mixture of two isomers in a 70:30 ratio: δ -143.2 ppm (d, d, J=50, 2.5 Hz, 30%) and δ -144.3 ppm (d, d, J=50, 2.5 Hz, 70%). cooled to 5° were simultaneously added at the same rate over 30 min. at about 10° with cooling after the addition the ether layer was separated washed with water dried (MgSO4) evaporated to dryness under reduced pressure The residue was recrystallized from benzene