Aluminium lithium hydride → HCID 25160587, compound

HRID 914025Notes

Reaction equation

HRID 914025 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]1([C:13]2([CH2:26][O:27][CH2:28][C:29]3[CH:30]=[C:31]([C:38]([F:41])([F:40])[F:39])[CH:32]=[C:33]4[C:37]=3[NH:36][CH:35]=[CH:34]4)[CH2:18][CH2:17][N:16]([C:19](OC(C)(C)C)=O)[CH2:15][CH2:14]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>O1CCCC1>[CH3:19][N:16]1[CH2:15][CH2:14][C:13]([CH2:26][O:27][CH2:28][C:29]2[CH:30]=[C:31]([C:38]([F:41])([F:39])[F:40])[CH:32]=[C:33]3[C:37]=2[NH:36][CH:35]=[CH:34]3)([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:18][CH2:17]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 57545939HCID 57545939, compound

Product 1

HCID 25160587HCID 25160587, compoundYield 67.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium aluminum hydride (1M in tetrahydrofuran, 1.71 ml, 1.71 mmol) was added to a solution of tert-butyl 4-phenyl-4-(((5-(trifluoromethyl)-1H-indol-7-yl)methoxy)methyl)piperidine-1-carboxylate (93 mg, 0.19 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 chromatographed on silica gel with 15% methanol in dichloromethane. The product 7-(((1-methyl-4-phenylpiperidin-4-yl)methoxy)methyl)-5-(trifluoromethyl)-1H-indole (52 mg, 0.129 mmol, 67.9% yield) was isolated as a clear oil. 1H-NMR (CDCl3, 400 MHz) δ 7.92 (bs, 1H), 7.78 (s, 1H), 7.32-7.48 (m, 5H), 7.08 (s, 1H), 6.85 (s, 1H), 6.45 (s, 1H), 4.72 (s, 2H), 3.52 (s, 2H), 2.73 (m, 2H), 2.31 (s, 3H), 2.22-2.40 (m, 4H), 2.12 (m, 2H); Mass spec. (MH)+: 403.11.

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 chromatographed on silica gel with 15% methanol in dichloromethane

Sources & evidence

ORD record
ord-4dbcb052de044c3eae1fd8de9a6948b8
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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