Ethyl Acetate → 4-chloro-6-(tetrahydro-2H-pyran-4-yl)pyrimidine

HRID 1842511Notes

Reaction equation

HRID 1842511 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[C:9]([O:12][CH2:13][CH3:14])(=O)[CH3:10].[Cl-].[NH4+].[CH3:17]C(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].[Zn]>[Cl:1][C:2]1[CH:7]=[C:6]([CH:17]2[CH2:14][CH2:13][O:12][CH2:9][CH2:10]2)[N:5]=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 31374DimethylacetamideHCID 709434,6-Dichloropyrimidine

Product 1

HCID 585484674-chloro-6-(tetrahydro-2H-pyran-4-yl)pyrimidineYield 14%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
80 °C

Procedure

A mixture of copper(I) iodide (0.067 g, 0.35 mmol), Pd(dppf)Cl2 (0.14 g, 0.18 mmol), and 4,6-dichloropyrimidine (0.52 g, 3.50 mmol) in DMA (3 mL) was placed under argon atmosphere using 3 evacuation/backfill cycles. The zinc reagent prepared in Step 1a above (4.5 mL, about 4.5 mmol) 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 4-chloro-6-(tetrahydro-2H-pyran-4-yl)pyrimidine (0.13 g, 0.64 mmol, 14% 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-68f787e0a0054395b7cdab42a543bba0
Source dataset
uspto-grants-2015_02
Patent number
US08946230B2

Reaction notes

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