3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanal → 4-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3,3-dimethyl-4-phenylbutan-2-ol
Reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:18]([CH3:22])([CH3:21])[CH:19]=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:29][Mg]Br>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)[C:18]([CH3:22])([CH3:21])[CH:19]([OH:20])[CH3:29])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1Participants
4
Procedure
To a solution of 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanal (from Ex 116(b), 25 mg, 0.067 mmol) in THF (1 ml) at 0° C. was added a solution of 1.4 M methylmagnesium bromide in 1 ml of THF (1.4 M) dropwise. After 1 hr, the reaction was quenched with sat. NH4Cl and was extracted with ethyl acetate. The organic phase was washed, dried over MgSO4, filtered, and concentrated to give 4-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3,3-dimethyl-4-phenylbutan-2-ol as a white solid (24 mg, 92% yield). It is a mixture of diastereomers in a 1:1 ratio. 1H NMR (400 MHz, MeOD) δ ppm 8.20 (1 H, d, J=5.09 Hz) 7.96 (1 H, d, J=9.16 Hz) 7.68-7.75 (2 H, m) 7.59-7.67 (2 H, m) 7.53 (2 H, dd, J=7.63, 2.54 Hz) 7.23-7.35 (4 H, m) 7.14-7.20 (1 H, m) 4.40 (1 H, s) 3.50-3.60 (1 H, m) 1.10 (3 H, 2 singlets,) 1.05 (3 H, s) 0.99 (3 H, 2 singlets). LC/MS (m/z) 389.3 [(M+1)+]; HPLC Rt: 3.96 min.