Methanol → 7-Benzyl-4,7-diazaspiro[2.5]octane

HRID 1951907Notes

Reaction equation

HRID 1951907 reaction equation
B.O1CC[CH2:4][CH2:3]1.O1CCCC1.ClC1C=CC([C@H]2N3C(SC(C(N4[CH2:47][C@H:46](F)[CH2:45][C@H:33]4[C:34]([N:36]4[CH2:43][C:40]5([CH2:42][CH2:41]5)[NH:39][CH2:38][C@@H:37]4C)=O)=O)=C3C(C)C)=N[C@]2(C2C=NC(Cl)=CC=2)C)=CC=1F.CO>C(OCC)(=O)C>[CH2:34]([N:36]1[CH2:43][C:40]2([CH2:41][CH2:42]2)[NH:39][CH2:38][CH2:37]1)[C:33]1[CH:45]=[CH:46][CH:47]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 2723981Borane;tetrahydrofuranHCID 46840819HCID 46840819, compound

Product 1

HCID 585423257-Benzyl-4,7-diazaspiro[2.5]octaneYield 59.2%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A borane-tetrahydrofuran complex (0.93 M tetrahydrofuran solution) (375 ml, 0.35 mol) was added to a tetrahydrofuran (200 ml) solution of the compound (20 g, 86.8 mmol) obtained in Step 2 above under ice cooling and then the resulting mixture was heated to reflux for 19 hours. Methanol (130 ml) was added to the reaction mixture under ice cooling, the resulting mixture was stirred for 60 minutes and then the solvent was concentrated under reduced pressure. Ethanol (450 ml), water (150 ml), and triethylamine (150 ml) were added to the residue obtained, the resulting mixture was heated to reflux for 2 hours and then the solvent was concentrated under reduced pressure. The residue obtained was diluted with ethyl acetate, washed with saturated aqueous sodium bicarbonate solution and saturated brine, and then dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was purified by silica gel column chromatography [chloroform:methanol=10:1 (v/v)] to give the title compound (10.4 g, 59%) as a colorless oil.

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux for 19 hours
  3. concentrationthe solvent was concentrated under reduced pressure
  4. additionEthanol (450 ml), water (150 ml), and triethylamine (150 ml) were added to the residue
  5. customobtained
  6. temperaturethe resulting mixture was heated
  7. temperatureto reflux for 2 hours
  8. concentrationthe solvent was concentrated under reduced pressure
  9. customThe residue obtained
  10. washwashed with saturated aqueous sodium bicarbonate solution and saturated brine
  11. dry with materialdried over anhydrous sodium sulfate
  12. customThe solvent was evaporated under reduced pressure
  13. customthe residue obtained
  14. customwas purified by silica gel column chromatography [chloroform:methanol=10:1 (v/v)]

Sources & evidence

ORD record
ord-ba8f595c6bc4487aa2562dab5beb985b
Source dataset
uspto-grants-2013_03
Patent number
US08404691B2

Reaction notes

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