Ethyl Acetate → 2-chloro-3-(tetrahydro-2H-pyran-4-yl)pyrazine

HRID 1842515Notes

Reaction equation

HRID 1842515 reaction equation
Cl[C:2]1[C:7]([Cl:8])=[N:6][CH:5]=[CH:4][N:3]=1.[I-].[O:10]1[CH2:15][CH2:14][CH:13]([Zn+])[CH2:12][CH2:11]1.C(OCC)(=O)C.[Cl-].[NH4+]>CC(N(C)C)=O.[Cu]I.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:8][C:7]1[C:2]([CH:13]2[CH2:14][CH2:15][O:10][CH2:11][CH2:12]2)=[N:3][CH:4]=[CH:5][N:6]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 785752,3-DichloropyrazineHCID 178506619HCID 178506619, compound

Product 1

HCID 585484362-chloro-3-(tetrahydro-2H-pyran-4-yl)pyrazineYield 29.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of copper(I) iodide (0.066 g, 0.35 mmol), Pd(dppf)Cl2 (0.14 g, 0.18 mmol), and 2,3-dichloropyrazine (0.52 g, 3.50 mmol) in DMA (3 mL) was placed under argon atmosphere using 3 evacuation/backfill cycles. A solution of (tetrahydro-2H-pyran-4-yl)zinc(II) iodide (about 3.50 mmol, prepared in example 6, step 1) was added dropwise via syringe and the mixture was heated to 80° C. for 4 h, then cooled to RT. Ethyl acetate and saturated aqueous ammonium chloride were added, the resulting layers were separated, and the organic layer was washed with water (2×), brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to give an oil. The oil was purified by silica gel chromatography to give 2-chloro-3-(tetrahydro-2H-pyran-4-yl)pyrazine (0.20 g, 1.03 mmol, 29% yield) as a light yellow solid.

Workup

  1. temperaturecooled to RT
  2. customthe resulting layers were separated
  3. washthe organic layer was washed with water (2×), brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oil
  8. customThe oil was purified by silica gel chromatography

Sources & evidence

ORD record
ord-2a9eeb61865b4b779519fd2138b8f01c
Source dataset
uspto-grants-2015_02
Patent number
US08946230B2

Reaction notes

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