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

HRID 967933Notes

Reaction equation

HRID 967933 reaction equation
[O:1]([C:8]1[CH:9]=[C:10]([N:14]2[CH2:22][CH2:21][C:16]3([NH:20][CH2:19][CH2:18][CH2:17]3)[CH2:15]2)[CH:11]=[N:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[C:25](=O)(O)[O-].[Na+]>C(O)=O>[CH3:25][N:20]1[C:16]2([CH2:21][CH2:22][N:14]([C:10]3[CH:11]=[N:12][CH:13]=[C:8]([O:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[CH:9]=3)[CH2:15]2)[CH2:17][CH2:18][CH2:19]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 115438947-(5-Phenoxy-3-pyridyl)-1,7-diazaspiro[4,4]nonane

Product 1

HCID 222911921-Methyl-7-(5-phenoxypyridin-3-yl)-1,7-diazaspiro[4.4]nonaneYield 90.9%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

To a stirring solution of 7-(5-phenoxy-3-pyridyl)-1,7-diazaspiro[4.4]nonane (420 mg, 1.42 mmol) in 37% aqueous solution of formaldehyde (5 mL) was added 98% formic acid (3 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 thick brown viscous liquid. This was distilled using a Kugelrohr apparatus (2 mm, 180° C.) to give a very pale cream-colored syrup (400 mg, 90.9%).

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 thick brown viscous liquid
  8. distillationThis was distilled
  9. customa Kugelrohr apparatus (2 mm, 180° C.)

Sources & evidence

ORD record
ord-5f8ed34f101b4800969cd6d68c28dfe4
Source dataset
uspto-grants-2005_10
Patent number
US06956042B2

Reaction notes

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