Z-VAL-NH2

To a stuffed solution of compound I (10 g, 39.84 mmol, 1 eq) in DMF (100 mL) was added DIPEA (19.7 mL, 119.5 mmol, 3 eq) and HATU (18.17 g, 47.8 mmol, 1.2 eq) at 0°C and the resulting mixture was stuffed for 15 mm. To the mixture was added ammonium chloride (10.7 g, 199.2 mmol, 5 eq) and the resulting mixture was allowed to stir at 23°C for another 16 h. The mixture was poured into ice cold water (500 mL), the organic components were extracted with EtOAc (3 x 500 mL) and the combined organic layers were washed with aqueous ammonium chloride solution and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to dryness. The crude product was recrystallized from ethanol to obtain the title compound (9.8 g, 98percent) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) ö 7.35 (m, 6H), 7.12 (d, 1H, J = 9 Hz), 7.01 (s, 1H), 5.03 (s, 2H), 3.80 (t, 1H, J = 8 Hz), 1.95 (m, 1H), 0.85 (m, 6H). LCMS: mlz = 251.2 [M+Hj , RT = 2.81 minutes, (Program P1, Column Y).General procedure: To a colorless solution of 150mg (0.50mmol) of Cbz-L-Phe-OH 3a in 10mL of THF were added 67μL (0.70mmol, 1.4equiv) of ClCOStep 1. To a solution of 27-1 (8 g, 31.8 mmol) and EtTo a solution of (S)-2-(benzyloxycarbonylamino)-3-methylbutanoic acid (10.0 g, 39.84 mmol) in 1, 4-dioxane (50 mL) was added di-tert-butyl dicarbonate (11.95 g, 51.79mmol) in portions at 0°C. Then pyridine (2 mL, 25.76 mmol) was added drop-wise at 0°C, followed by ammonium bicarbonate (3.94 g, 50.43 mmol) in portions. The reaction was stirred at room temperature overnight. The mixture was poured into ice water and filtered. The filter cake was washed with water and dried under vacuum. The filter cake was then re-crystallized from dioxane/water (80 mL, 9: 1, v/v) to give (S)-benzyl (1-amino-3-methyl-1-oxobutan-2-yl)carbamate(5.3 g, 53.15percent yield) as a white solid. LC-MS (ESI) found: 251 [M+Hf’, ee>99percent, (CHIRALPAK AS-H, 15percent ethanol/ hexane)

Molecular Weight:250.29
XLogP3:1.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:6
Exact Mass:250.13174244
Monoisotopic Mass:250.13174244
Topological Polar Surface Area:81.4
Heavy Atom Count:18
Complexity:286
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes