(R)-tert-Butyl 3-(aminomethyl)morpholine-4-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution (0.3 M) of tert-butyl 3-cyano-4-morpholinecarboxylate (prepared as described in the J. Med. Chem. 2007, 50, 4953-4975) in MeOH was added PtO2 (0.1 eq) and the mixture was stirred O/N under an H2 atmosphere at 50 psi. The reaction mixture was filtered and concentrated under reduced pressure to afford the title compound RR1. MS (ES) C10H20N2O3 required: 216, found: 217 (M+H)+. The reaction mixture was filtered concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following the general procedure for Intermediate 2 using 4-fluoro-3-nitro-N,N-bis(2,2,2-trifluoroethyl)benzamide (213 mg, 0.612 mmol) and tert-butyl 3-(aminomethyl)morpholine-4-carboxylate (160 mg, 0.734 mmol) in 10 mL of EtOH containing TEA (0.130 mL, 0.918 mmol). The product was purified by flash chromatography on silica gel using 2:1/hexanes:EtOAc as eluent. Yield: 304 mg (91%); 1H NMR (400 MHz, CHLOROFORM-D) δ 1.49 (s, 9H), 3.17 (m, 1H), 3.52 (m, 1H), 3.64 (m, 3H), 3.92 (m, 2H), 4.25 (q, J=8.20 Hz, 6H), 7.57 (d, J=8.59 Hz, 1H), 8.30 (d, J=1.95 Hz, 1H), 8.48 (m, 1H); MS (ESI) 544.75 (MH+). The product was purified by flash chromatography on silica gel using 2:1/hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Following the general procedure for Intermediate 2 using 4-fluoro-3-nitro-N,N-bis(2,2,2-trifluoroethyl)benzamide (213 mg, 0.612 mmol) and tert-butyl 3-(aminomethyl)morpholine-4-carboxylate (160 mg, 0.734 mmol) in 10 mL of EtOH containing TEA (0.130 mL, 0.918 mmol). The product was purified by flash chromatography on silica gel using 2:1/hexanes:EtOAc as eluent. Yield: 304 mg (91%); 1H NMR (400 MHz, CHLOROFORM-D) δ 1.49 (s, 9H), 3.17 (m, 1H), 3.52 (m, 1H), 3.64 (m, 3H), 3.92 (m, 2H), 4.25 (q, J=8.20 Hz, 6H), 7.57 (d, J=8.59 Hz, 1H), 8.30 (d, J=1.95 Hz, 1H), 8.48 (m, 1H); MS (ESI) 544.75 (MH+). The product was purified by flash chromatography on silica gel using 2:1/hexanes