1-(3,5-difluorophenyl)ethanamine

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: Following a similar procedure to that described in Example (1a), 2.0 g of 4-chlorophenyl 3-nitrophenyl ketone, 2.40 g of 1-(3,5-difluorophenyl)ethylamine, 4.26 ml of triethylamine, 1.01 ml of titanium tetrachloride, 3.02 g of sodium cyanoborohydride and 0.66 ml of acetic acid were reacted, to obtain 2.92 g of the title compound as a yellow oil. were reacted

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

Procedure: Following a similar procedure to that described in Example (1a), 850 mg of 3-nitrophenyl 4-isopropoxyphenyl ketone, 936 mg of 1-(3,5-difluorophenyl)ethylamine, 1.66 ml of triethylamine, 0.39 ml of titanium tetrachloride, 788 mg of sodium cyanoborohydride and 0.26 ml of acetic acid were reacted, to obtain 1.20 g of the title compound as a yellow oil. were reacted

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

Procedure: Following a similar procedure to that described in Example (1a), 790 mg of 3-nitrophenyl 4-propoxyphenyl ketone, 870 mg of 1-(3,5-difluorophenyl)ethylamine, 1.54 ml of triethylamine, 0.37 ml of titanium tetrachloride, 733 mg of sodium cyanoborohydride and 0.24 ml of acetic acid were reacted, to obtain 1.16 g of the title compound as a yellow oil. were reacted

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

Procedure: Following a similar procedure to that described in Example (1a), 790 mg of 3-nitrophenyl 4-propoxyphenyl ketone, 870 mg of 1-(3,5-difluorophenyl)ethylamine, 1.54 ml of triethylamine, 0.37 ml of titanium tetrachloride, 733 mg of sodium cyanoborohydride and 0.24 ml of acetic acid were reacted, to obtain 1.16 g of the title compound as a yellow oil. were reacted

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

Procedure: Following a similar procedure to that described in Example (1a), 1.0 g of 4-ethoxyphenyl 3-nitrophenyl ketone, 1.16 g of 1-(3,5-difluorophenyl)ethylamine, 2.01 ml of triethylamine, 0.49 ml of titanium tetrachloride, 975 mg of sodium cyanoborohydride and 0.32 ml of acetic acid were reacted, to obtain 1.41 g of the title compound as a yellow oil. were reacted

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

Procedure: Essentially following the procedures described in Intermediate 1 for methyl 1-aminocyclopentanecarboxylate hydrochloride, but using 1-aminocyclohexanecarboxylic acid in place of 1-aminocyclopentanecarboxylic acid, the title compound was obtained. MS: m/z=158 (M+1).

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

Procedure: To a stirred mixture of 3′,5′-difluoroacetophenone (86.8 g, 0.556 mol) and 2 M NH3 in EtOH (1.4 L, 2.8 mol) was added titanium(IV) isopropoxide (326 mL, 1.11 mol) dropwise over 15 min stirring was continued at ambient temperature for 20 h. The mixture was cooled in an ice-water bath and sodium borohydride (31.5 g, 0.834 mol) was added in portions over 60 min. The reaction mixture was stirred for an additional 1 h, and then quenched with aqueous NH4OH (2 M, 1.3 L) followed by EtOAc (1 L). The resulting mixture was aged for 18 h and filtered through a pad of celite, washing with EtOAc (1 L). To the filtrate was added EtOAc (2 L) and H2O (1 L) containing NaCl (ca. 100 g). The mixture was shaken and allowed to separate. The organic layer was concentrated in vacuo to a volume of about 500 mL and partitioned between EtOAc (2 L) and saturated aqueous Na2CO3 (300 mL). The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo to give the title compound. MS: m/z=182 (M+CH3CN−NH2). The mixture was cooled in an ice-water bath The reaction mixture was stirred for an additional 1 h quenched with aqueous NH4OH (2 M, 1.3 L) The resulting mixture was aged for 18 h filtered through a pad of celite washing with EtOAc (1 L) To the filtrate was added EtOAc (2 L) and H2O (1 L) containing NaCl (ca. 100 g) The mixture was shaken to separate The organic layer was concentrated in vacuo to a volume of about 500 mL partitioned between EtOAc (2 L) and saturated aqueous Na2CO3 (300 mL) The organic layer was dried (Na2SO4) filtered concentrated in vacuo

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

Procedure: The title compound, MS: m/e=446.1 (M+H+), was prepared in accordance with the general method of example 1 from 5-iodo-2-chloroquinoline, 7-amino-2,3-dihydro-2,2-dimethylbenzofuran (CAS 68298-46-4) and rac-1-(3,5-difluorophenyl)ethylamine.