Process for making beta 3 agonists and intermediates

A process of producing compound I-11 comprising:

• (a) reacting compound I-5b:
• with acetone and Boc2O to produce compound I-6:
• (b) oxidizing compound I-6 with an oxidizing agent in the presence of a solvent and a catalyst to produce compound I-7:
• (c) reacting compound I-7 with phosphate compound A-4:
• to produce compound I-8:
• wherein the reaction is carried out at a temperature of about 20 to 40° C. and in the presence of a solvent selected from the group consisting of THF, MTBE, CH2Cl2, MeCN, toluene and a mixture comprising two of the foregoing solvents;
• (d) reducing compound I-8 in the presence of a catalyst selected from the group consisting of Pd, Raney Ni, Pt, PdCl2, and Pd(OH)2 to produce compound I-9:
• (e) reacting compound I-9 with an acid to produce compound I-10:
• and
• (f) reducing compound I-10 in the presence of a catalyst to produce compound I-11:
• wherein P1 is Boc and P2 is selected from the group consisting of Ac, Bn, Boc, Bz, Cbz, DMPM, FMOC, Ns, Moz, and Ts.

A process of making a compound of Formula (I):

• comprising reacting compound I-11:
• with compound i-12 in the presence of a coupling reagent, a solvent and an acid:
• wherein the coupling agent is selected from the group consisting of CDI, DCC, EDC, EDC methiodide, T3P, HATU, HBTU and mix-anhydrides;
• and
• wherein the solvent is selected from the group consisting of MeOH, EtOH, IPA, n-PrOH, MeCN, DMF, DMAc, THF, EtOAc and IPAc.

A crystalline anhydrous form of compound of Formula I-11 characterized by XRPD by the following reflections with the d-spacing.

• Position [°2 Theta]
• d-spacing [Å]
• 17.8453
• 4.97
• 25.1979
• 3.53
• 20.1002
• 4.42
• 23.9931
• 3.71
• 16.7073
• 5.31
• 25.5483
• 3.49
• 19.6576
• 4.52
• 13.8883
• 6.38
• 28.086
• 3.18
• 20.6498
• 4.30

A crystalline hemihydrate form of compound of Formula I-11 characterized by XRPD by the following reflections with the d-spacing.

• Position [°2 Theta]
• d-spacing [Å]
• 17.9681
• 4.94
• 17.8666
• 4.96
• 23.1905
• 3.84
• 15.3049
• 5.79
• 19.7955
• 4.49
• 19.9483
• 4.45
• 23.1076
• 3.85
• 25.3415
• 3.51
• 16.0859
• 5.51
• 25.6746
• 3.47