Formaldehyde → HCID 23506708, compound

HRID 1740961Notes

Reaction equation

HRID 1740961 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]2[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]2[CH3:15])[CH:3]=1.C([Li])CCC.[O:21]1CCC[CH2:22]1.C=O>C(OCC)C.CCCCCC>[OH:21][CH2:22][CH2:8][C:6]1[N:5]=[C:4]([N:9]2[C:13]([CH3:14])=[CH:12][CH:11]=[C:10]2[CH3:15])[CH:3]=[C:2]([CH3:1])[CH:7]=1

Participants

7

Reactant 4

HCID 712Formaldehyde3×HCID 8028TetrahydrofuranHCID 224907362-(2,5-Dimethyl-1H-pyrrol-1-yl)-4,6-dimethylpyridineHCID 178418339Butyllithium

Product 1

HCID 23506708HCID 23506708, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-17.5 °C

Procedure

A solution of 2.97 mg (14.8 mmol) of 4,6-dimethyl-2-(2,5-dimethylpyrrol-1-yl)pyridine (from Example 53, Step A) in 15 mL of ethyl ether was added to a -20° C. solution prepared from 30 mL of ethyl ether and 12 mL (17 mmol) of 1.4 M n-butyllithium in hexane. The mixture was stirred for 1 h at -20 to -15° C. with the formation of a precipitate. Tetrahydrofuran (10 mL) was added, giving an orange-red solution of the intermediate anion. Paraformaldehyde in a separate flask was heated to 150-160° C., generating formaldehyde gas. The formaldehyde, diluted with nitrogen, was introduced as a gas stream impinging on the anion solution (kept at -15 to -10° C.) until the anion color had faded (20-30 min). The mixture was stirred an additional 15 min, quenched by the addition of 50 mL of saturated aqueous ammonium chloride, and extracted with 50 mL of ethyl acetate. The organic layer was washed with 30 mL of saturated aqueous sodium choride, dried (sodium sulfate), decanted, and evaporated. The residue was purified by flash column chromatography on 90 g of silica gel eluting with 2 L of 30% ethyl acetate in hexane to give 1.55 g (45% yield) of 6-(2-hydroxyethyl)-4-methyl-2-(2,5-dimethylpyrrol-1-yl)pyridine as a colorless oil.

Workup

  1. customgiving an orange-red solution of the intermediate anion
  2. additionwas introduced as a gas stream impinging on the anion solution (kept at -15 to -10° C.) until the anion color
  3. custom(20-30 min)
  4. stirringThe mixture was stirred an additional 15 min
  5. customquenched by the addition of 50 mL of saturated aqueous ammonium chloride
  6. extractionextracted with 50 mL of ethyl acetate
  7. washThe organic layer was washed with 30 mL of saturated aqueous sodium choride
  8. dry with materialdried (sodium sulfate)
  9. customdecanted
  10. customevaporated
  11. customThe residue was purified by flash column chromatography on 90 g of silica gel eluting with 2 L of 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-f603ac9e767240daa9d3b05c5ad5586c
Source dataset
uspto-grants-1999_10
Patent number
US05972975

Reaction notes

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