3,4-dihydro-2H-pyran → beta(R)-[[(tetrahydropyran-2-yl)oxy]methyl]-beta(2-fluorophenyl)-propionitrile

HRID 566264Notes

Reaction equation

HRID 566264 reaction equation
[OH:1][CH2:2][C@@H:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[F:13])[CH2:4][C:5]#[N:6].[O:14]1[CH:19]=[CH:18][CH2:17][CH2:16][CH2:15]1.O=P(Cl)(Cl)Cl>CCOCC>[O:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH:15]1[O:1][CH2:2][C@@H:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[F:13])[CH2:4][C:5]#[N:6]

Participants

5

Reactant 3

HCID 80803,4-dihydro-2H-pyranHCID 24813Phosphorus oxychlorideHCID 109976222-fluoro-beta(R)-(hydroxymethyl)benzenepropionitrile

Product 1

HCID 70217065beta(R)-[[(tetrahydropyran-2-yl)oxy]methyl]-beta(2-fluorophenyl)-propionitrile

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of β(R)-(hydroxymethyl)-β-(2-fluorophenyl)-propionitrile (210 g, 1.18 mol) in Et2O (200 ml), is added 3,4-dihydro-2H-pyran (225 ml, 2.68 mol) at ambient temperature. The mixture is stirred for 5 minutes and POCl3 (5 mL) is added dropwise. The reaction mixture is stirred for 30 minutes at ambient temperature and then refluxed for 2 hours. The resulting solution is allowed to cool and the solvent is removed in vacuo. The residue is then chromatographed (EtOAc/hexane, 1:4) to give β(R)-[[(tetrahydropyran-2-yl)oxy]methyl]-β(2- fluorophenyl)-propionitrile as an oil.

Workup

  1. stirringThe reaction mixture is stirred for 30 minutes at ambient temperature
  2. temperaturerefluxed for 2 hours
  3. temperatureto cool
  4. customthe solvent is removed in vacuo
  5. customThe residue is then chromatographed (EtOAc/hexane, 1:4)

Sources & evidence

ORD record
ord-ee0c590e8b9f4f298c511792dadc88da
Source dataset
uspto-grants-2001_01
Patent number
US06174888B1

Reaction notes

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