Aluminium lithium hydride → HCID 58215575, compound

HRID 593547Notes

Reaction equation

HRID 593547 reaction equation
C([O:3][C:4](=O)[CH2:5][O:6][CH2:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([Cl:17])=[CH:14][CH:15]=2)[C:10]([CH3:18])=[C:9]1[C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[Cl:17][C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([CH2:7][O:6][CH2:5][CH2:4][OH:3])[C:9]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1)=[C:10]2[CH3:18]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 58215663HCID 58215663, compound

Product 1

HCID 58215575HCID 58215575, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A flask is charged with (5-chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethoxy)-acetic acid ethyl ester (Example 72b, 1.00 g, 2.79 mmol) and THF (10 mL). The reaction mixture is cooled to 0° C. and lithium aluminum hydride (1M in THF, 6.98 mL, 6.98 mmol) is added. After stirring for 1 h at room temperature, the mixture is quenched with water (0.3 mL), followed with 16% aqueous NaOH (0.3 mL). Water (1 mL) is added and stirring is continued for 10 min. The solids are filtered off and the filtrate is concentrated in vacuo. The residue is purified by silica gel flash chromatography (dichloromethane-acetonitrile, 3:1), followed by a purification on Chiralcel® IA column (heptane-EtOH, 9:1) to afford 2-(5-chloro-3-methyl-2-pyridin-3-yl-indol-1-ylmethoxy)-ethanol as a white solid. 1H NMR (400 MHz, MeOD) δ ppm 2.27 (s, 3H), 3.42-3.49 (m, 2H), 3.60 (t, J=4.8 Hz, 2H), 5.47 (s, 2H), 7.27 (dd, J=8.7, 1.9 Hz, 1H), 7.57-7.62 (m, 2H), 7.64 (dd, J=8.0, 4.9 Hz, 1H), 8.10 (dt, J=7.8, 1.9 Hz, 1H), 8.66 (dd, J=4.9, 1.6 Hz, 1H), 8.74 (d, J=1.3 Hz, 1H). HRMS (ESI) m/z 317.1056 [(M+H)+ Calcd for C17H17ClN2O2: 317.1507].

Workup

  1. customthe mixture is quenched with water (0.3 mL)
  2. additionWater (1 mL) is added
  3. stirringstirring
  4. waitis continued for 10 min
  5. filtrationThe solids are filtered off
  6. concentrationthe filtrate is concentrated in vacuo
  7. customThe residue is purified by silica gel flash chromatography (dichloromethane-acetonitrile, 3:1)
  8. customfollowed by a purification on Chiralcel® IA column (heptane-EtOH, 9:1)

Sources & evidence

ORD record
ord-318d95342bac48c68ec48d3991dedee6
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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