Methanol → 2-(Diphenylmethyl)-5-oxa-2,8-diazaspiro[3.5]nonane

HRID 1689271Notes

Reaction equation

HRID 1689271 reaction equation
CSC.B.[CH:5]([N:18]1[CH2:21][C:20]2([CH2:26][NH:25][C:24](=O)[CH2:23][O:22]2)[CH2:19]1)([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CO.CNCCNC>C1COCC1>[CH:5]([N:18]1[CH2:21][C:20]2([CH2:26][NH:25][CH2:24][CH2:23][O:22]2)[CH2:19]1)([C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8070N,N'-DimethylethylenediamineHCID 12423031(Dimethyl sulfide)trihydroboronHCID 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 1

HCID 8028TetrahydrofuranSolvent

Procedure

Borane methyl sulfide complex (2M in THF, 10.7 mL) was added to a solution of 2-benzhydryl-5-oxa-2,8-diazaspiro[3.5]nonan-7-one (example 33, step e) (2 g) in dry THF (40 mL) and the resultant solution was stirred at 70° C. under nitrogen for 50 minutes. The mixture was cooled to room temperature and treated dropwise with methanol (40 mL) followed by N1,N2-dimethylethane-1,2-diamine (3.43 g). The mixture was heated at 70° C. for 6 hours. The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and brine. The organic layer was dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography using 1% triethylamine and 5% methanol in dichloromethane as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 1.35 g.

Workup

  1. temperatureThe mixture was heated at 70° C. for 6 hours
  2. customThe solvent was removed under reduced pressure
  3. customthe residue partitioned between ethyl acetate and brine
  4. dry with materialThe organic layer was dried over sodium sulphate
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customThe crude product was purified by flash silica chromatography
  8. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-3ec69db7bfa74476b03033f4afc05426
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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