Triphenylphosphine → 2-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyridine

HRID 1842509Notes

Reaction equation

HRID 1842509 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[O:20]1[CH2:25][CH2:24][CH:23]([OH:26])[CH2:22][CH2:21]1.[Cl:27][C:28]1[CH:33]=[C:32](O)[CH:31]=[CH:30][N:29]=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1.C(OCC)(=O)C>[Cl:27][C:28]1[CH:33]=[C:32]([O:26][CH:23]2[CH2:24][CH2:25][O:20][CH2:21][CH2:22]2)[CH:31]=[CH:30][N:29]=1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 74956Tetrahydro-4H-pyran-4-olHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 178516507HCID 178516507, compound

Product 1

HCID 585484652-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyridineYield 83%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

Triphenylphosphine (6.88 g, 26.2 mmol) was added to a mixture of tetrahydro-2H-pyran-4-ol (2.68 g, 26.2 mmol) and 2-chloropyridin-4-ol (2.72 g, 21.00 mmol) in THF (70 mL) under argon. Diisopropyl azodicarboxylate (DIAD) (5.28 mL, 26.9 mmol) was added dropwise over 5 mins and then the mixture was heated to 55° C. overnight. The mixture was cooled to RT and the solvent was removed in vacuo to give an oil. The oil was purified by silica gel chromatography to give crude 2-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyridine as an oil. This material was dissolved in ethyl acetate and then washed with 1N aqueous sodium hydroxide, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give 2-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyridine (3.71 g, 17.4 mmol, 83% yield) as a light yellow solid.

Workup

  1. temperatureThe mixture was cooled to RT
  2. customthe solvent was removed in vacuo
  3. customto give an oil
  4. customThe oil was purified by silica gel chromatography
  5. customto give crude 2-chloro-4-(tetrahydro-2H-pyran-4-yloxy)pyridine as an oil
  6. washwashed with 1N aqueous sodium hydroxide
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-085722b2bb3745a788968ac7bc9ddeeb
Source dataset
uspto-grants-2015_02
Patent number
US08946230B2

Reaction notes

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