Aluminium lithium hydride → 1-(diphenylmethyl)-3-{[(1-methylethyl)amino]methyl}-N-(phenylmethyl)azetidin-3-amine

HRID 1808979Notes

Reaction equation

HRID 1808979 reaction equation
[C:1]1([CH:7]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:8]2[CH2:11][C:10]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)([C:12]([NH:14][CH:15]([CH3:17])[CH3:16])=O)[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[C:26]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]2[CH2:11][C:10]([CH2:12][NH:14][CH:15]([CH3:17])[CH3:16])([NH:18][CH2:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:9]2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 670518131-(diphenylmethyl)-N-(1-methylethyl)-3-[(phenylmethyl)amino]azetidine-3-carboxamide

Product 1

HCID 670515751-(diphenylmethyl)-3-{[(1-methylethyl)amino]methyl}-N-(phenylmethyl)azetidin-3-amineYield 90.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of the 1-(diphenylmethyl)-N-(1-methylethyl)-3-[(phenylmethyl)amino]azetidine-3-carboxamide (0.40 g, 0.97 mmol) in tetrahydrofuran (10 mL) at room was added a solution of lithium aluminum hydride in tetrahydrofuran (1M, 2.90 mL, 2.90 mmol), and the resulting mixture was stirred at 50° C. for 3 h. The reaction mixture was cooled to room temperature, quenched with 20% aqueous hydroxide solution (1 mL), diluted with ether (50 mL) and filtered. The filtrate was washed with brine solution (20 mL each), dried over sodium sulfate, filtered and concentrated to give an oily residue which was purified by flash chromatography (silica gel, eluting with 5% methanol-dichloromethane) to give 1-(diphenylmethyl)-3-{[(1-methylethyl)amino]methyl}-N-(phenylmethyl)azetidin-3-amine (0.35 g, 90% yield), 1H NMR (400 MHz, CDCl3): 7.42-7.14 (m, 15H), 4.34 (s, 1H), 3.66 (s, 2H), 3.22-3.18 (d, 2H), 2.97 (s, 2H), 2.90-2.86 (d, 2H), 2.68-2.62 (p, 1H), 1.09-1.07 (d, 6H); MS (EI) for C27H33N3: 400 (MH+).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched with 20% aqueous hydroxide solution (1 mL)
  3. additiondiluted with ether (50 mL)
  4. filtrationfiltered
  5. washThe filtrate was washed with brine solution (20 mL each)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give an oily residue which
  10. customwas purified by flash chromatography (silica gel, eluting with 5% methanol-dichloromethane)

Sources & evidence

ORD record
ord-366894f061ab4cd7a7eba90fc70a24b4
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

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