Formaldehyde → 7-(5-Ethoxypyridin-3-yl)-1-methyl-1,7-diazaspiro[4.4]nonane

HRID 2076406Notes

Reaction equation

HRID 2076406 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([N:10]2[CH2:18][CH2:17][C:12]3([NH:16][CH2:15][CH2:14][CH2:13]3)[CH2:11]2)[CH:7]=[N:8][CH:9]=1)[CH3:2].C=O.[C:21](=O)(O)[O-].[Na+]>C(O)=O>[CH3:21][N:16]1[C:12]2([CH2:17][CH2:18][N:10]([C:6]3[CH:7]=[N:8][CH:9]=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=3)[CH2:11]2)[CH2:13][CH2:14][CH2:15]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 222912427-(5-Ethoxypyridin-3-yl)-1,7-diazaspiro[4.4]nonane

Product 1

HCID 222912187-(5-Ethoxypyridin-3-yl)-1-methyl-1,7-diazaspiro[4.4]nonaneYield 89.3%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

To a stirring solution of 7-(5-ethoxy-3-pyridyl)-1,7-diazaspiro[4.4]nonane (360.4 mg, 1.4 mmol) in 37% aqueous solution of formaldehyde (4 mL) was added 98% formic acid (2 mL) under nitrogen. The reaction mixture was heated to reflux for 8 h. The reaction mixture was cooled to room temperature, then basified with saturated aqueous sodium bicarbonate to pH 8-9 and extracted with chloroform (4×15 mL). The combined chloroform extracts were dried (Na2SO4), filtered and concentrated by rotary evaporation to afford a viscous brown liquid. This was distilled using a Kugelrohr apparatus (2 mm, 180° C.) to give a very light cream-colored syrup (340 mg, 89.3%).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 8 h
  3. extractionextracted with chloroform (4×15 mL)
  4. dry with materialThe combined chloroform extracts were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation
  7. customto afford a viscous brown liquid
  8. distillationThis was distilled
  9. customa Kugelrohr apparatus (2 mm, 180° C.)

Sources & evidence

ORD record
ord-645a7cac09414a5398f9ff6f58c495bf
Source dataset
uspto-grants-2011_04
Patent number
US07923559B2

Reaction notes

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