3-(diethoxyphosphorylmethyl)aniline

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

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

Procedure: Following the procedure described in part E of Example 1 (R), (S)-α-[[2-[((1,1-dimethylethyl)dimethylsilyl)oxy]-2-[4-hydroxy-3-[(methylsulfonyl)amino]phenyl]ethyl]amino]-4-methoxybenzeneacetic acid was condensed with diethyl 3-aminobenzylphosphonate to generate the title compound. The diethyl 3-aminobenzylphosphonate was prepared by sequential treatment of commercial 3-nitrobenzyl bromide with triethyl phosphite at 125° C. for 6 hours followed by reduction with Na2S2 O4 in THF/H2O at 100° C.

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

Procedure: A solution of the diethyl (3-nitrobenzyl)phosphonate prepared as described above, in MeOH (5 mL) was hydrogenated in the presence of 10% Pd/C (100 mg) overnight. The reaction mixture was filtered and the filtrate concentrated in vacuo to afford the desired product diethyl (3-aminobenzyl)phosphonate (0.690 g; yield: 95%), which was used directly in further chemistries without purification. 1H-NMR (CDCl3, 400 MHz): δ=1.24 (t, J=7.2 Hz, 6H), 3.04 (d, J=21.6 Hz, 2 H), 3.66 (s, br, 2 H), 4.01 (q, J=7.2 Hz, 4 H), 6.57 (d, J=8.8 Hz, 1 H), 6.67-6.68 (m, 2 H), 7.08 (t, J=7.6 Hz, 1 H). MS (ES+): m/z 244.00 (MH+). HPLC: tR=2.24 min (ZQ3, polar—5 min). The reaction mixture was filtered the filtrate concentrated in vacuo

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

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

Procedure: A solution of the diethyl(3-nitrobenzyl)phosphonate prepared as described above, in MeOH (5 mL) was hydrogenated in the presence of 10% Pd/C (100 mg) overnight. The reaction mixture was filtered and the filtrate concentrated in vacuo to afford the desired product diethyl(3-aminobenzyl)phosphonate (0.690 g; yield: 95%), which was used directly in further chemistries without purification. 1H-NMR (CDCl3, 400 MHz): δ=1.24 (t, J=7.2 Hz, 6H), 3.04 (d, J=21.6 Hz, 2H), 3.66 (s, br, 2H), 4.01 (q, J=7.2 Hz, 4H), 6.57 (d, J=8.8 Hz, 1H), 6.67-6.68 (m, 2H), 7.08 (t, J=7.6 Hz, 1H). MS (ES+): m/z 244.00 (MH+). HPLC: tR=2.24 min (ZQ3, polar—5 min). The reaction mixture was filtered the filtrate concentrated in vacuo

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

Procedure: Following the procedure described in part E of Example 1 (R), (S)-α-[[2-[((1,1-dimethylethyl)dimethylsilyl)oxy]-2-[4-hydroxy-3-[(methylsulfonyl)amino]phenyl]ethyl]amino]-4-methoxybenzeneacetic acid was condensed with diethyl 3-aminobenzylphosphonate to generate the title compound. The diethyl 3-aminobenzylphosphonate was prepared by sequential treatment of commercial 3-nitrobenzyl bromide with triethyl phosphite at 125° C. for 6 hours followed by reduction with Na2S2 O4 in THF/H2O at 100° C.

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

Procedure: A solution of the diethyl (3-nitrobenzyl)phosphonate prepared as described above, in MeOH (5 mL) was hydrogenated in the presence of 10% Pd/C (100 mg) overnight. The reaction mixture was filtered and the filtrate concentrated in vacuo to afford the desired product diethyl (3-aminobenzyl)phosphonate (0.690 g; yield: 95%), which was used directly in further chemistries without purification. 1H-NMR (CDCl3, 400 MHz): δ=1.24 (t, J=7.2 Hz, 6H), 3.04 (d, J=21.6 Hz, 2 H), 3.66 (s, br, 2 H), 4.01 (q, J=7.2 Hz, 4 H), 6.57 (d, J=8.8 Hz, 1 H), 6.67-6.68 (m, 2 H), 7.08 (t, J=7.6 Hz, 1 H). MS (ES+): m/z 244.00 (MH+). HPLC: tR=2.24 min (ZQ3, polar—5 min). The reaction mixture was filtered the filtrate concentrated in vacuo

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