Reaction Steps
By a procedure similar to Lova-HA, atorvastatin (168 mg, 0.31 mmol, in the lactone form) was treated with MgBr2 (115 mg, 0.62 mmol), hydroxylamine hydrochloride (184 mg, 2.6 mmol), and sodium bicarbonate (209 mg, 2.5 mmol) in anhydrous THF/MeOH (7:3, 1 mL) at ambient temperature for 20 h to give Atorva-HA (91 mg, 51%). The purity was 95% as shown by HPLC analysis on an HC—C18 column (Agilent, 4.6×250 mm, 5 Gm), tR=14.8 min (gradients of 30-100% aqueous CH3CN in 30 min). C33H36FN3O5; colorless oil; [α]26D=−1.3 (EtOAc, c=1.0); TLC (CH2Cl2/MeOH (9:1)) Rf=0.33; IR νmax (neat) 3405, 3301, 3059, 2960, 2926, 1738, 1657, 1595, 1527, 1508, 1436, 1314, 1241, 1223, 1157, 1108, 1078, 1046, 843, 753, 692 cm−1; 1H NMR (DMSO-d6, 400 MHz) δ 10.31 (1H, br s), 9.77 (1H, br s), 8.68 (1H, br s), 7.50 (2H, d, J=7.6 Hz), 7.18-7.24 (6H, m), 7.07 (4H, br s), 6.98-7.00 (2H, m), 4.69 (1H, br s), 4.60 (1H, d, J=4.0 Hz), 3.92-3.95 (1H, m), 3.72-3.83 (2H, m), 3.53 (1H, br s), 3.21-3.25 (1H, m), 2.01 (2H, d, J=6.0 Hz), 1.63 (1H, br s), 1.53 (1H, br s), 1.28-1.38 (8H, m) ppm; 13C NMR (DMSO-d6, 100 MHz) δ 167.4, 166.1, 162.8, 160.3, 139.4, 135.9, 134.9, 133.4, 129.1 (2×), 128.7, 128.4 (2×), 127.6 (2×), 127.3, 125.3, 122.9, 120.6, 119.4 (2×), 117.5, 115.4, 115.2, 66.0, 65.6, 43.8, 40.9, 40.7, 25.6, 22.3 (2×) ppm; ESI-HRMS (negative mode) calcd. for C33H35FN3O5: 572.2561. found: m/z 572.2562 [M−H]−.
