2-Benzhydryl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one → 2-(Diphenylmethyl)-5-oxa-2,8-diazaspiro[3.5]nonane

HRID 446479Notes

Reaction equation

HRID 446479 reaction equation
[CH:1]([N:14]1[CH2:17][C:16]2([CH2:22][NH:21][C:20](=O)[CH2:19][O:18]2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C1COCC1.CCCC(C)C>[CH:1]([N:14]1[CH2:17][C:16]2([CH2:22][NH:21][CH2:20][CH2:19][O:18]2)[CH2:15]1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

4

Reactant 1

HCID 579892642-Benzhydryl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one

Product 1

HCID 579892372-(Diphenylmethyl)-5-oxa-2,8-diazaspiro[3.5]nonane

Reagents, catalysts & solvents 2

HCID 78922-MethylpentaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Borane-methyl sulfide complex in THF (13.38 mL) was added in one portion to 2-benzhydryl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one (2.5 g) (WO2009098448, example 33, step e) in THF (50 mL) at room temperature under argon. The resulting solution was stirred at reflux for 90 minutes. The reaction was cooled to room temperature then the reaction mixture was quenched with methanol (50.0 mL). N,N′-Dimethylethylenediamine (5.18 mL) was added and the reaction mixture allowed to stir at room temperature for 1 week. The reaction mixture was evaporated to dryness and re-dissolved in ethyl acetate (250 mL), and washed with water (250 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was dissolved in iso-hexane (10 mL) and was purified by flash silica chromatography, eluting with 10% methanolic ammonia in DCM. Pure fractions were evaporated to dryness to afford 2-benzhydryl-5-oxa-2,8-diazaspiro[3.5]nonane. Yield 1.647 g.

Workup

  1. temperatureat reflux for 90 minutes
  2. customthe reaction mixture was quenched with methanol (50.0 mL)
  3. additionN,N′-Dimethylethylenediamine (5.18 mL) was added
  4. stirringto stir at room temperature for 1 week
  5. customThe reaction mixture was evaporated to dryness
  6. dissolutionre-dissolved in ethyl acetate (250 mL)
  7. washwashed with water (250 mL)
  8. dry with materialThe organic layer was dried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customto afford crude product
  12. customwas purified by flash silica chromatography
  13. washeluting with 10% methanolic ammonia in DCM
  14. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-0768c6333c5847c9bb810a94463a890e
Source dataset
uspto-grants-2013_07
Patent number
US08476265B2

Reaction notes

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