Aluminium lithium hydride → HCID 25160586, compound

HRID 914026Notes

Reaction equation

HRID 914026 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:39]([F:42])([F:41])[F:40])=[CH:14][C:15]=2[CH2:17][O:18][CH2:19][C:20]2([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:25][CH2:24][N:23]([C:26](OC(C)(C)C)=O)[CH2:22][CH2:21]2)[CH:10]=[CH:9]1>O1CCCC1>[CH3:7][N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:39]([F:41])([F:42])[F:40])=[CH:14][C:15]=2[CH2:17][O:18][CH2:19][C:20]2([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:21][CH2:22][N:23]([CH3:26])[CH2:24][CH2:25]2)[CH:10]=[CH:9]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 57545984HCID 57545984, compound

Product 1

HCID 25160586HCID 25160586, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium aluminum hydride (1M in tetrahydrofuran, 1.07 ml, 1.07 mmol) was added to a solution of tert-butyl 4-(((1-methyl-5-(trifluoromethyl)-1H-indol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (60 mg, 0.119 mmol) in tetrahydrofuran (5 ml). The reaction was heated at reflux for 3 h. The reaction was quenched by sequential dropwise addition of water (0.2 mL), 1N sodium hydroxide (0.6 mL), and more water (0.2 mL). The mixture was filtered and the filtrate evaporated. The residue was purified by chromatography on silica gel with a gradient from 5% to 10% 2M ammonia in methanol/dichloromethane. The product 1-methyl-7-(((1-methyl-4-phenylpiperidin-4-yl)methoxy)methyl)-5-(trifluoromethyl)-1H-indole (45 mg, 0.108 mmol, 91% yield) was isolated as a clear oil. 1H-NMR (CDCl3, 400 MHz) δ 7.82 (s, 1H), 7.22-7.36 (m, 6H), 6.93 (s, 1H), 6.49 (s, 1H), 4.65 (s, 2H), 3.63 (s, 3H), 3.42 (s, 2H), 2.53 (m, 2H), 2.20 (s, 3H), 2.13-2.25 (m, 4H), 1.94 (m, 2H); Mass spec. (MH)+: 417.13.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 3 h
  3. customThe reaction was quenched by sequential dropwise addition of water (0.2 mL), 1N sodium hydroxide (0.6 mL), and more water (0.2 mL)
  4. filtrationThe mixture was filtered
  5. customthe filtrate evaporated
  6. customThe residue was purified by chromatography on silica gel with a gradient from 5% to 10% 2M ammonia in methanol/dichloromethane

Sources & evidence

ORD record
ord-7a29fe0969bc4db8aaa26d717471fbbe
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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