Potassium Iodide → 4-{4-[(1-isopropylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-carbonitrile

HRID 273078Notes

Reaction equation

HRID 273078 reaction equation
Cl.Cl[CH2:3][CH:4]1[CH2:7][N:6]([CH:8]([CH3:10])[CH3:9])[CH2:5]1.[OH:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2([C:24]#[N:25])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CN(C=O)C>[CH:8]([N:6]1[CH2:7][CH:4]([CH2:3][O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3([C:24]#[N:25])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:14][CH:13]=2)[CH2:5]1)([CH3:10])[CH3:9]

Participants

6

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 230916094-(4-Hydroxy-phenyl)-tetrahydro-pyran-4-carbonitrileHCID 68579065HCID 68579065, compound

Product 1

HCID 598374014-{4-[(1-isopropylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-carbonitrileYield 60.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(chloromethyl)-1-isopropylazetidine hydrochloride (2.8 g, 15.2 mmol), 4-(4-hydroxyphenyl)tetrahydropyran-4-carbonitrile (3.1 g, 15.2 mmol) and potassium carbonate (8.5 g, 61.6 mmol) were combined in DMF (40 ml) and stirred at 500 for 2 hours. Potassium iodide (0.5 g 3.0 mmol) was added and the mixture was stirred at 50° for 18 hours then at 90-95° for a further 5 hours. The reaction mixture was concentrated in vacuo then partitioned between ethyl acetate (80 ml) and water (50 ml). The ethyl acetate was washed with saturated NaCl (50 ml) then dried over Na2SO4 and concentrated in vacuo to give a brown semi-crystalline material which was triturated with diisopropyl ether (25 ml) to give the title compound as a beige powder (2.9 g, 60%). 1H NMR (400 MHz, CDCl3) δ7.38 (d, 2H), 6.91 (d, 2H), 4.08 (m, 4H), 3.89 (m, 2H), 3.41 (t, 2H), 3.02 (t, 2H), 2.87 (m, 1H), 2.31 (m, 1H), 2.15-2.00 (m, 4H), 0.94 (d, 6H).

Workup

  1. stirringthe mixture was stirred at 50° for 18 hours
  2. waitat 90-95° for a further 5 hours
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthen partitioned between ethyl acetate (80 ml) and water (50 ml)
  5. washThe ethyl acetate was washed with saturated NaCl (50 ml)
  6. dry with materialthen dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customto give a brown semi-crystalline material which
  9. customwas triturated with diisopropyl ether (25 ml)

Sources & evidence

ORD record
ord-5f8a5fee1a294e6689badaa9c69fa8ab
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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