MK 886 → 3-[1-(p-Chlorobenzyl)-3-(t-butylthio)-5-(i-propyl)-indole-2-yl]-2,2-dimethylpropanol
Reaction equation
[Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]([CH3:18])[CH3:17])=[CH:13][CH:14]=3)[C:9]([S:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[C:8]2[CH2:24][C:25]([CH3:30])([CH3:29])[C:26](O)=[O:27])=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]([CH3:18])[CH3:17])=[CH:13][CH:14]=3)[C:9]([S:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[C:8]2[CH2:24][C:25]([CH3:30])([CH3:29])[CH2:26][OH:27])=[CH:31][CH:32]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 200 mg of methyl 1-(p-chlorobenzyl)-3-(t-butylthio)-α,α-dimethyl-5-(i-propyl)-indole-2-propanoate (from Example 25) in 1.5 mL tetrahydrofuran (THF) was added 0.4 ml of a solution of lithium aluminum hydride (1.0 M in THF) at 0° C. After 2h at 0° C., the reaction mixture was quenched with saturated aqueous Na2SO4, diluted with ether and stirred at room temperature for 1 h. The resultant slurry was filtered and the filtrate concentrated to dryness. The resultant oil was purified by flash chromatography (eluant: hexane-ethyl acetate, 8:2) to give the title compound as a viscous oil. 1H NMR (250 MHz, Acetone D ) δ: 0.94 (s, 9H), 1.26 (s, 6H), 1.27 (d, 2H J=7.0 Hz), 2.95-3.08 (m, 2H), 2.99 (septuplet, 1H, J=7.0 Hz), 3.27 (d, 2H, J=7.0 Hz), 4.02 (t, 1H, J=7.0 Hz, exchanges with D20), 4.69 (broad s, 2H), 6.92 (d, 2H, J=8.5 Hz), 7.00 (dd, 1H, J=7.5 and 2.0 Hz), 7.24 (d, 1H, J=7.5 Hz); 7.29 (d, 2H, J=8.5 Hz), 7.58 (d, 1H, J=2.0 Hz) IR (CDCl3) 3420 cm-1.