Hydrochloric Acid → 2-[[4-(2-Pyrimidinyl)phenyl]methoxy]acetaldehyde

HRID 1166138Notes

Reaction equation

HRID 1166138 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][OH:14])=[CH:9][CH:8]=1.[H-].[Na+].[CH2:17]([O:19]C(OCC)CBr)[CH3:18].Cl.[OH-].[Na+]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]=1[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][O:14][CH2:18][CH:17]=[O:19])=[CH:9][CH:8]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 24758Sodium hydride2×HCID 74852Ethane, 2-bromo-1,1-diethoxy-2×HCID 15597455[4-(Pyrimidin-2-yl)phenyl]methanol

Product 1

HCID 858230842-[[4-(2-Pyrimidinyl)phenyl]methoxy]acetaldehydeYield 12%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of the product from step A (559 mg, 3.00 mmol) in DMF (4 mL) was added dropwise to a suspension of sodium hydride (60% in mineral oil, 144 mg, 3.60 mmol) at 0° C. The solution was stirred for 30 min at 0° C., bromoacetaldehyde diethyl acetal (0.55 mL, 3.66 mmol) and tetrabutylammonium iodide (111 mg, 0.30 mmol) were added, and the resulting mixture was stirred at 70° C. for 12 h. Additional sodium hydride (60% in mineral oil, 70 mg, 1.75 mmol) and bromoacetaldehyde diethyl acetal (0.55 mL, 3.66 mmol) were added and heating at 70° C. was continued for 12 h. The reaction mixture was concentrated, the residue was diluted with water and extracted with ethyl acetate, the combined organic layers were dried (MgSO4), and concentrated. Purification by chromatography (SiO2, 1:1 hexane/ethyl acetate) gave material which was taken up in ethanol (2 mL) and 10% aq. HCl (10 mL) and stirred for 12 h. The reaction mixture was made basic with aq. NaOH, extracted with ethyl acetate, dried (MgSO4), and concentrated. Purification by chromatography (SiO2, 1:1 hexane/ethyl acetate) provided 80 mg (12%) of the title compound. MS 229 (M+H)+.

Workup

  1. stirringthe resulting mixture was stirred at 70° C. for 12 h
  2. temperatureheating at 70° C.
  3. waitwas continued for 12 h
  4. concentrationThe reaction mixture was concentrated
  5. additionthe residue was diluted with water
  6. extractionextracted with ethyl acetate
  7. dry with materialthe combined organic layers were dried (MgSO4)
  8. concentrationconcentrated
  9. customPurification by chromatography (SiO2, 1:1 hexane/ethyl acetate)
  10. customgave material which
  11. extractionextracted with ethyl acetate
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated
  14. customPurification by chromatography (SiO2, 1:1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-20fedd54d32a4627b814b2c4da6af2a9
Source dataset
uspto-grants-2003_09
Patent number
US06613747B2

Reaction notes

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