Aluminum(III) Chloride → 4-(benzyloxy)-1-ethyl-6-fluoro-3-(2-(isoindolin-2-yl)ethyl)-1H-indole

HRID 1404132Notes

Reaction equation

HRID 1404132 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[Cl-].[Cl-].[Cl-].[Al+3].[CH2:11]([O:18][C:19]1[CH:27]=[C:26]([F:28])[CH:25]=[C:24]2[C:20]=1[C:21]([CH2:31][C:32]([N:34]1[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH2:35]1)=O)=[CH:22][N:23]2[CH2:29][CH3:30])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1COCC1>[CH2:11]([O:18][C:19]1[CH:27]=[C:26]([F:28])[CH:25]=[C:24]2[C:20]=1[C:21]([CH2:31][CH2:32][N:34]1[CH2:35][C:36]3[C:41](=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH2:42]1)=[CH:22][N:23]2[CH2:29][CH3:30])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 6451240Aluminum(III) ChlorideHCID 21226445Aluminium lithium hydrideHCID 672350282-(4-(benzyloxy)-1-ethyl-6-fluoro-1H-indol-3-yl)-1-(isoindolin-2-yl)ethanone

Product 1

HCID 509963494-(benzyloxy)-1-ethyl-6-fluoro-3-(2-(isoindolin-2-yl)ethyl)-1H-indoleYield 57.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of LiAlH4 (100 mg, 2.6 mmol) in THF (30 mL) was added aluminum trichloride (463 mg, 3.51 mmol) at 0° C. After stirring for 10 min, a solution of 31-2 (180 mg, 0.42 mmol) in THF (5 mL) was added dropwise. The reaction mixture was stirred for 5 min before Na2SO4.10H2O was added to quench the reaction. The solid was filtered off and the filtrate was evaporated. The resulting residue was purified on silica gel column chromatography eluting with dichloromethane/methanol (10:1) to get 31-3 (100 mg, 57%) as a yellow solid. 1H-NMR (400 MHz, CDCl3): δ (ppm) 7.46 (d, J=7.2 Hz, 2H), 7.31-7.26 (m, 4H), 7.27 (t, J=3.6 Hz, 1H), 7.09-7.06 (m, 2H), 6.93 (s, 1H), 6.65 (d, J=7.2 Hz, 1H), 6.42 (d, J=7.2 Hz, 1H), 5.06 (s, 2H), 4.02-4.00 (m, 6H), 3.27 (s, 4H), 1.41 (t, J=7.4 Hz, 3H). LRMS: calc 414.2 and found: 414.9 [M+1].

Workup

  1. additionwas added
  2. customto quench
  3. customthe reaction
  4. filtrationThe solid was filtered off
  5. customthe filtrate was evaporated
  6. customThe resulting residue was purified on silica gel column chromatography
  7. washeluting with dichloromethane/methanol (10:1)

Sources & evidence

ORD record
ord-998fd6208eeb4d178cfd2370d2e38aa9
Source dataset
uspto-grants-2014_12
Patent number
US08912220B2

Reaction notes

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