Aluminium lithium hydride → 1-(4-{4-[(1-isopropylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-yl)methanamine

HRID 273079Notes

Reaction equation

HRID 273079 reaction equation
[CH:1]([N:4]1[CH2:7][CH:6]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([C:22]#[N:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5]1)([CH3:3])[CH3:2].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH:1]([N:4]1[CH2:7][CH:6]([CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH2:22][NH2:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5]1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 598374014-{4-[(1-isopropylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-carbonitrile

Product 1

HCID 598375291-(4-{4-[(1-isopropylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-yl)methanamineYield 98.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-{4-[(1-isopropylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-carbonitrile (1.8 g, 5.73 mmol) in THF (80 ml) was cooled to 0° C. under an atmosphere of nitrogen. A solution of lithium aluminium hydride (1.0M solution in Et2O, 17 ml, 17 mmol) was added dropwise over 5 min. The mixture was stirred whilst warming to ambient temperature over 18 hours. The reaction was cooled to 0° C. and quenched with water (0.5 ml) then 2M NaOH (0.5 ml) and then water (1.5 ml). Celite® (3 g) was added and the mixture stirred at ambient temperature for 0.5 hour. Diluted with ethyl acetate (50 ml), filtered and concentrated in vacuo to give a colourless oil (1.8 g). The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (97:3:0.3 to 88:12:1.2 by volume) to give the title compound as a white crystalline solid (1.55 g, 85%). 1H NMR (400 MHz, CDCl3) δ 7.18 (d, 2H), 6.89 (d, 2H), 4.18 (d, 2H), 3.77 (m, 2H), 3.54 (m, 2H), 3.41 (t, 2H), 3.02 (t, 2H), 2.88 (m, 1H), 2.75 (s, 2H), 2.31 (quintet, 1H), 2.11 (m, 2H), 1.80 (m, 2H), 0.95 (d, 6H). LRMS ESI+ m/z 319 [M+H]+. HRMS ESI+ m/z 319.2375 [MH]+.

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. customquenched with water (0.5 ml)
  3. additionCelite® (3 g) was added
  4. stirringthe mixture stirred at ambient temperature for 0.5 hour
  5. additionDiluted with ethyl acetate (50 ml)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2a253d9243034652ae1792f0321ca282
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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