N-Cbz-O-Benzyl-L-threonine

White powder

To a stirred solution of Int-B (2.21g, 6.44 mmol) in DCM (30 mL) were added N-methyl morpholine (2.6 g, 25.81 mmol), 1-Propanephosphonic anhydride solution (50 wt. percent in ethyl acetate) (8.2 g, 25.81 mmol) and racemic tert-butyl l-oxo-2, 5, 8-triazaspiro[3.5]nonane-8- carboxylate (EH) (1 g, 6.45 mmol) at 0 °C under nitrogen atmosphere. The reaction mixture was brought to RT and stirred for 16 h. After consumption of the starting material (by TLC), the reaction was diluted with water (50 mL) and extracted with 10percent MeOH/ DCM (3 x 50 mL). Combined organic layer was dried over Na2S04 and concentrated to obtain crude material which was purified by column chromatography by eluting 10percent MeOH/DCM to afford racemic compound 6 (350 mg, 12percent) as an off white solid. The racemic was separated by chiral HPLC purification and obtained 130 mg of compound 6-F1 and 60 mg of compound 6-F2. Compound 6-F1: 1H-NMR: (400 MHz, DMSO- ): delta 7.87 (s, 1H), 7.35-7.24 (m, 11H), 5.08-5.00 (m, 2H), 4.56- 4.46 (m, 3H), 3.91 (d, / = 12.4 Hz, 1H), 3.73-3.71 (m, 1H), 3.22 (d, / = 5.2 Hz, 1H), 3.17 (d, / = 4.8 Hz, 1H), 3.04-2.99 (m , 1H), 2.77 (d, 7 = 11.6 Hz, 1H), 2.64 (d, / = 12.0 Hz, 1H), 2.18- 2.13 (m, 4H), 1.88-1.83 (m, 1H), 1.11 (d, / = 6.4 Hz, 3H). Compound 6-F2: 1H-NMR: (400 MHz, DMSO-ifc): delta 7.88 (s, 1H), 7.42 (d, / = 9.2 Hz, 1H), 7.35-7.25 (m, 10H), 5.08-5.01 (m, 2H), 4.63-4.44 (m, 3H), 3.97 (d, / = 12.8 Hz, 1H), 3.85-3.82 (m, 1H), 3.23 (d, / = 5.2 Hz, 1H), 3.07 (d, / = 4.4 Hz, 1H), 3.05-3.02 (m , 1H), 2.77 (d, / = 12.0 Hz, 1H), 2.69 (d, / = 11.6 Hz, 1H), 2.120-2.13 (m, 4H), 1.98 -1.91 (m, 1H), 1.12 (d, / = 6.4 Hz, 3H).To a stirred solution of Int-A (1.7g, 4.98 mmol) in DCM (50 mL) were added N-methyl morpholine (2.51 g, 24.89 mmol), 1-Propanephosphonic anhydride solution (50 wt. percent in ethyl acetate) (7.9 g, 24.89 mmol) and racemic tert-butyl l-oxo-2, 5, 8-triazaspiro[3.5]nonane-8- carboxylate (EB-racemic) (1 g, 4.15 mmol) at 0 C under nitrogen atmosphere. The reaction mixture was brought to RT and stirred for 16 h. After consumption of the starting material (by TLC), the reaction was diluted with water (50 mL) and extracted with DCM (3 x 50 mL). Combined organic layer was dried over Na2S04 and concentrated to obtain crude material which was purified by column chromatography by eluting 10percent MeOH/ DCM to afford racemic compound 5 (700 mg, 30percent) as an off white solid. The racemic was separated by chiral HPLC purification and obtained 80 mg each of compound 5-Fl and compound 5-F2. Compound 5-Fl: 1H-NMR: (400 MHz, DMSO-ifc):5 7.99 (s, 1H), 7.42-7.24 (m, 11H), 5.04 (t, / = 14.0 Hz, 2H), 4.55-4.48 (m, 3H), 3.80-3.71 (m, 4H), 3.43 (d, / = 14.0 Hz, 1H), 3.43 (d, / = 4.0 Hz, 1H), 3.32- 3.30 (m, 2H), 3.00 (br s, 1H), 1.40 (s, 9H), 1.12 (d, / = 6.4 Hz, 3H). Compound 5-F2: 1H-NMR: (400 MHz, DMSO-i):5 7.96 (s, 1H), 7.35-7.25 (m, 11H), 5.08-5.01 (dd, / = 16.8, 12.8 Hz, 2H), 4.69-466 (dd, / = 8.8, 5.6 Hz, 1H), 3.54 (d, / = 12.0 Hz, 1H), 3.44 (d, / = 12.0 Hz, 1H), 3.86-3.74 (m, 4H), 3.43 (m, 1H), 3.39 (d, / = 5.4 Hz, 1H), 3.29-3.27 (m, 2H), 2.94 (br s, 1H), 1.39 (s, 9H), 1.12 (d, / = 6.4 Hz, 3H).

Molecular Weight:343.4
XLogP3:2.8
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:9
Exact Mass:343.14197277
Monoisotopic Mass:343.14197277
Topological Polar Surface Area:84.9
Heavy Atom Count:25
Complexity:416
Defined Atom Stereocenter Count:2
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes