In an open vessel, tert-butyl 5-chloro-2-(1H-tetrazol-1-yl)benzylcarbamate (14 g, 45.20 mmol, prepared as described in J. Med. Chem. 2004, 47, 2995, was suspended in acetonitrile (80 mL). HCl (6 M aqueous solution, 37.7 mL, 225.99 mmol) was added and the mixture was then stirred at room temperature for 4 hours. Water (200 mL) and TBME (100 mL) were added. To the aqueous phase and under ice-cooling was added EtOAc (200 mL) followed by slow addition of 2 M NaOH (aq., 130 mL). The organic phase was then washed with water (100 mL). To the EtOAc solution (220 mL) containing the crude (5-chloro-2-(1H-tetrazol-1-yl)phenyl)methanamine was then added (5S)-1-[(2R)-2-(4-fluorophenyl)-2-hydroxyacetyl]-4,5-dihydro-1H-pyrazole-5-carboxylic acid (7.53 g, 28.28 mmol) followed by the addition of N-methylmorpholine (4.66 mL, 42.43 mmol). To this clear homogenous solution was then added TBTU (10.90 g, 33.94 mmol) in one portion. The mixture was then stirred at room temperature over night. The precipitate formed was filtrated and then washed with TBME (100 mL). After drying in vacuo, the desired compound was obtained as a solid (7.65 g, 59%). The mother liquor was diluted with EtOAc and washed with Na2CO3 (aq., sat), water and 1 M HCl (aq.). Crystallization from CH3CN/water gave 4.59 g of the title compound. Total yield 88%. 1H NMR (600 MHz, CD3CN) δ 2.93 (ddd, 1H), 3.10 (ddd, 1H), 4.15-4.19 (m, 2H), 4.25 (dd, 1H), 4.60 (dd, 1H), 5.73-5.76 (m, 1H), 6.97-6.99 (m, 1H), 7.07-7.10 (m, 2H), 7.28-7.30 (m, 1H), 7.42-7.46 (m, 3H), 7.54-7.56 (m, 1H), 7.71 (d, 1H), 9.20 (s, 1H).
