Diisobutylaluminum hydride → (5-Chloro-3-methyl-2-pyridin-3-yl-indol-1-yl)-methanol

HRID 1661586Notes

Reaction equation

HRID 1661586 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

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 582155992,2-Dimethyl-propionic acid 5-chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethyl ester

Product 1

HCID 58215766(5-Chloro-3-methyl-2-pyridin-3-yl-indol-1-yl)-methanol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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

  1. customThe reaction is quenched with MeOH (1 mL)
  2. washwashed with saturated aqueous sodium potassium tartrate
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give a residue which
  7. customis purified by silica gel flash chromatography (heptane-ethyl acetate, 3:7)

Sources & evidence

ORD record
ord-3f2d11337f0749a19b8d82419441cf2f
Source dataset
uspto-grants-2011_10
Patent number
US08030334B2

Reaction notes

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