Diisobutylaluminum hydride → (5-Chloro-3-methyl-2-pyridin-3-yl-indol-1-yl)-methanol
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][O:12]C(=O)C(C)(C)C)[C:6]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1)=[C:5]2[CH3:25].CC(C[AlH]CC(C)C)C>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][OH:12])[C:6]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1)=[C:5]2[CH3:25]Participants
Conditions
- Temperature
- -78 °C
Procedure
A flask is charged with 2,2-dimethyl-propionic acid 5-chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl ester (Example 65, 0.607 g, 1.684 mmol) and dichloromethane (10 mL) and cooled to −78° C. DIBAL-H (1M in hexane, 4.21 mL, 4.21 mmol) is added and the mixture is stirred at −78° C. for 1 h. The reaction is quenched with MeOH (1 mL) and then washed with saturated aqueous sodium potassium tartrate and extracted with ethyl acetate. The organic layer is dried over sodium sulfate and concentrated in vacuo, to give a residue which is purified by silica gel flash chromatography (heptane-ethyl acetate, 3:7) to afford (5-chloro-3-methyl-2-pyridin-3-yl-indol-1-yl)-methanol as a white color solid. 1H NMR (400 MHz, MeOD) δ ppm 2.27 (s, 3H), 5.46 (s, 2H), 7.25 (dd, J=8.6, 2.0 Hz, 1H), 7.55 (s, 1H), 7.58 (s, 1H), 7.59 (d, J=2.0 Hz, 1H), 7.62-7.67 (m, 1H), 8.08 (dt, J=8.1, 2.0, 1.8 Hz, 1H), 8.66 (dd, J=4.9, 1.6 Hz, 1H), 8.75 (d, J=1.3 Hz, 1H). HRMS (ESI) m/z 273.0807 [(M+H)+ Calcd for C15H14ClN2O: 273.0795].
Workup
- customThe reaction is quenched with MeOH (1 mL)
- washwashed with saturated aqueous sodium potassium tartrate
- extractionextracted with ethyl acetate
- dry with materialThe organic layer is dried over sodium sulfate
- concentrationconcentrated in vacuo
- customto give a residue which
- customis purified by silica gel flash chromatography (heptane-ethyl acetate, 3:7)
Sources & evidence
- ORD record
- ord-ae369117cd7a4697bc69be4e86431aed
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09242963B2
Reaction notes
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