Water → HCID 11270195, compound

Participants

Reaction Conditions

Reaction Steps

The product from Example 1 (37.1 g) in toluene (1.8L) under N2 in a 3L 3-necked flask equipped with an overhead mechanical stirrer, addition funnel, and temperature probe was treated with diisobutylaluminum hydride in heptane (132 mL) dropwise at −78° C. over 40 minutes. After complete addition, the reaction mixture was stirred at −78° C. and monitored by HPLC, Zorbax Rx-C8 4.6 mm×25 cm column; mobile phase 90% H2O (0.1% H3PO4):10% CH3CN (0.1% H3PO4) to 30:70 over 15 minutes, then to 10:90 over 20 minutes before ramping back to 10:90 over 2 minutes; 45 minute run; flow rate of 1 mL/minute; UV detection at 225 nm. Retention times: starting material—29.9 minutes; product—20.4 minutes, and/or TLC, EtOAc:heptane (2:3), until starting material was consumed, about 1 hour. Ethyl acetate (500 mL) was added to quench any excess DIBAL, cooling was removed and saturated Rochelle's salt solution (1L) was added. The quenched mixture warmed to room temperature with stirring. The stirring was continued until layers clearly separated. The organic layer was washed with brine (500 mL) before concentrating to a solid. The isolated solid was dried at 40° C. in a vacuum oven to yield 41.2 g of the title compound as a tan solid which was used in the next step without further purification. A small reference sample was crystallized from CH3CN. Anal. calcd for C25H33NO3Si: C, 70.88; H, 7.85; N, 3.31. Found: C, 70.60; H, 7.84; N, 3.22; 1H NMR [(CD3)2SO] δ0.10 (3H, s), 0.97 (9H, s), 1.08 (3H, s), 1.26 (3H, s), 2.24 (3H, s), 5.41 (1H, br), 6.07 (1H, br),6.55˜6.61 (4H, m), 6.91(1H, d), 6.98 (1H, t), 7.99 (1H, d); 13C NMR [(CD3)2SO] δ−4.5, −4.2, 18.0,22.8, 25.8, 25.8, 28.2, 30.1, 49.7, 89.9, 111.2, 113.5, 113.7, 115.7, 116.4, 116.9, 126.2, 127.2, 128.2, 130.2, 132.4, 145.3, 151.0, 151.8 with 2 peaks overlapping; HRMS-FAB: calcd m/z 423.2230, found 423.2232.

Provenance & Evidence