Water → 1-(4-{4-[(1-cyclobutylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-yl)methanamine

HRID 273062Notes

Reaction equation

HRID 273062 reaction equation
[CH:1]1([N:5]2[CH2:8][CH:7]([CH2:9][O:10][C:11]3[CH:16]=[CH:15][C:14]([C:17]4([C:23]#[N:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>C1COCC1>[CH:1]1([N:5]2[CH2:8][CH:7]([CH2:9][O:10][C:11]3[CH:16]=[CH:15][C:14]([C:17]4([CH2:23][NH2:24])[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[CH2:6]2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 598374294-{4-[(1-cyclobutylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-carbonitrile

Product 1

HCID 598374711-(4-{4-[(1-cyclobutylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-yl)methanamineYield 59.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

4-{4-[(1-cyclobutylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-carbonitrile (0.29 g, 0.89 mmol), was dissolved in THF (5 mL). The solution was cooled to 0° C. under nitrogen. Lithium aluminiumhydride (2.7 mL, 1.0M solution in diethyl ether) was added dropwise. The reaction was stirred at 0° C. for 30 minutes, then warmed up to ambient temperature for 4 hours under a nitrogen atmosphere until complete. The reaction was cooled to 0° C., water (0.1 mL) was added dropwise followed by sodium hydroxide (2.0M, 0.1 mL) and water (0.3 mL). The mixture was filtered (using dichloromethane:methanol (90:10)) through celite. The organics were dried over sodium sulphate, filtered and concentrated in vacuo to provide a clear oil. This was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 to 90:10:1) to provide the title compound (0.175 g, 59%) as a clear colourless oil. 1H NMR (400 MHz, CDCl3) δ 1.60-1.70 (m, 2H), 1.70-1.85 (m, 2H), 1.85-1.95 (m, 2H), 1.95-2.06 (m, 2H), 2.1-2.18 (m, 2H), 2.79 (s, 2H), 2.9 (m, 1H), 3.1 (t, 2H), 3.2 (m, 1H), 3.48 (m, 2H), 3.54 (m, 2H), 3.8 (m, 2H), 4.10 (d, 2H), 6.9 (d, 2H), 7.2 (d, 2H). HRMS ESI+ m/z 331.2374 [MH]+.

Workup

  1. temperaturewarmed up to ambient temperature for 4 hours under a nitrogen atmosphere until complete
  2. temperatureThe reaction was cooled to 0° C.
  3. filtrationThe mixture was filtered (using dichloromethane:methanol (90:10)) through celite
  4. dry with materialThe organics were dried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto provide a clear oil
  8. customThis was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 to 90:10:1)

Sources & evidence

ORD record
ord-4c1cdc67b9b845ac92e81de30e134db9
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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