4-Chlorophenol → 4-((4-Chlorophenoxy)methyl)-2-(methylthio)pyrimidine

HRID 2059851Notes

Reaction equation

HRID 2059851 reaction equation
[CH3:1][S:2][C:3]1[N:8]=[C:7]([CH2:9][OH:10])[CH:6]=[CH:5][N:4]=1.[Cl:11][C:12]1[CH:17]=[CH:16][C:15](O)=[CH:14][CH:13]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[Cl:11][C:12]1[CH:17]=[CH:16][C:15]([O:10][CH2:9][C:7]2[CH:6]=[CH:5][N:4]=[C:3]([S:2][CH3:1])[N:8]=2)=[CH:14][CH:13]=1

Participants

6

Reactant 4

HCID 46844-ChlorophenolHCID 11776TriphenylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 14270868(2-(Methylthio)pyrimidin-4-yl)methanol

Product 1

HCID 585798424-((4-Chlorophenoxy)methyl)-2-(methylthio)pyrimidineYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (2-(methylthio)pyrimidin-4-yl)methanol (US 2005/0148610) (0.515 g, 3.30 mmol), 4-chlorophenol (0.466 g, 3.63 mmol), and triphenylphosphine (1.297 g, 4.95 mmol) in THF (10 mL) was added a solution of 1,1′-(azodicarbonyl)dipiperidine (1.248 g, 4.95 mmol) in THF (10 mL) dropwise. After stirring the reaction at RT overnight, the solids were filtered. The filtrate was diluted with EtOAc (30 mL), washed with water (20 mL) and by brine. The organic phase was dried (Na2SO4) and concentrated to afford the crude product. The crude product was purified using flash chromatography (silica gel/hexanes-ethyl acetate 100:0 to 0:100 gradient) to afford the desired product 4-((4-chlorophenoxy)methyl)-2-(methylthio)pyrimidine 6A (0.825 g, 3.09 mmol, 94% yield) as a light yellow solid. 1H NMR (400 MHz, Chloroform-D) δ 8.45 (1H, d, J=5.02 Hz), 7.18 (2H, d, J=8.78 Hz), 7.07-7.13 (1H, m), 6.80 (2H, d, J=8.78 Hz), 4.99 (2H, s), 2.51 (3H, s).

Workup

  1. customthe reaction at RT overnight
  2. filtrationthe solids were filtered
  3. additionThe filtrate was diluted with EtOAc (30 mL)
  4. washwashed with water (20 mL) and by brine
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. concentrationconcentrated
  7. customto afford the crude product
  8. customThe crude product was purified

Sources & evidence

ORD record
ord-f3cff234b9d543068ebcc72e44e6e883
Source dataset
uspto-grants-2012_10
Patent number
US08278316B2

Reaction notes

Loading…