3-(2-fluorophenyl)propan-1-amine

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

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

Procedure: Coupling of ketone 5 and 3-(2-fluorophenyl)-1-propylamine, using the method given in Example 1, gave 6-{trans-4-[3-(2-fluorophenyl)propylamino]-cyclohexyl}-3H-benzoxazol-2-one (1.7 g, 45%) as the HCl salt: 1H NMR (500 MHz, DMSO-d6): δ 11.50 (s, 1H), 8.86 (s, 2H), 7.34 (t, J=8 Hz, 1H), 7.35-7.26 (m, 1H), 7.19-7.15 (m, 3H), 7.02-6.97 (m, 2H), 3.10-3.03 (m, 1H), 2.98-2.92 (m, 2H), 2.72 (dd, J=8, 8 Hz, 2H), 2.57-2.50 (m, 1H), 2.18-2.13 (m, 2H), 1.98-1.92 (m, 2H), 1.89-1.85 (m, 2H), 1.57-1.46 (m, 4H).

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 3-(2-fluorophenyl)-propylamine (306 mg, 2 mmol), 2-bromomethyl-benzoic acid methyl ester (458 mg, 2 mmol), and K2CO3 (200 mg, 1.45 mmol) in toluene (10 mL) was heated with stirring at 100° C. for 16 h. Workup and silica gel column chromatography using a gradient of hexanes to 50% ethyl acetate in hexanes afforded 2-[3-(2-fluorophenyl)-propyl]-2,3-dihydroisoindol-1-one (275 mg, 51%). GC/MS gave: m/z (rel.int.) 269 (M+, 32), 147 (89), 146 (100), 119 (29), 109 (25) and 91 (40). was heated

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

Procedure: A solution of 3-(2-fluorophenyl) propionitrile (9.11 g) in tetrahydrofuran (200 mL) was heated to reflux and treated with borane-methyl sulfide complex (6 mL of ˜10 M, 60 mmol). Approximately half of the volume of the reaction was then distilled off. The mixture was then cooled in a −15° C. bath and treated dropwise with ice water (100 mL). The mixture was then concentrated to a solid. The solid was then dissolved in water (100 mL) and treated with concentrated (12 N)HCl (50 mL). The mixture was heated at reflux for 1 h, cooled to ambient temperature, and equilibrated with diethyl ether (100 mL). The organic solution was removed and the resulting aqueous mixture, cooled by the addition of ice, and then basified (pH>10) by treatment with 10 N NaOH (70 mL). The resulting solution was extracted with diethyl ether (100 mL). The diethyl ether extract was removed, dried over anhydrous MgSO4, filtered and concentrated to afford 3-(2-fluorophenyl)propylamine (3.62 g (41% from 2-fluorobenzaldehyde)). GC/MS gave: m/z (rel.int.) 153 (M+, 10), 136 (100), 109 (50), and 83 (22). to reflux treated with borane-methyl sulfide complex (6 mL of ˜10 M, 60 mmol) Approximately half of the volume of the reaction was then distilled off treated dropwise with ice water (100 mL) The mixture was then concentrated to a solid The solid was then dissolved in water (100 mL) treated with concentrated (12 N)HCl (50 mL) The mixture was heated at reflux for 1 h cooled to ambient temperature The organic solution was removed the resulting aqueous mixture, cooled by the addition of ice The resulting solution was extracted with diethyl ether (100 mL) The diethyl ether extract was removed dried over anhydrous MgSO4 filtered concentrated

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

Procedure: Coupling of ketone 5 and 3-(2-fluorophenyl)-1-propylamine, using the method given in Example 1, gave 6-{trans-4-[3-(2-fluorophenyl)propylamino]-cyclohexyl}-3H-benzoxazol-2-one (1.7 g, 45%) as the HCl salt: 1H NMR (500 MHz, DMSO-d6): δ 11.50 (s, 1H), 8.86 (s, 2H), 7.34 (t, J=8 Hz, 1H), 7.35-7.26 (m, 1H), 7.19-7.15 (m, 3H), 7.02-6.97 (m, 2H), 3.10-3.03 (m, 1H), 2.98-2.92 (m, 2H), 2.72 (dd, J=8, 8 Hz, 2H), 2.57-2.50 (m, 1H), 2.18-2.13 (m, 2H), 1.98-1.92 (m, 2H), 1.89-1.85 (m, 2H), 1.57-1.46 (m, 4H).