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

HRID 471040Notes

Reaction equation

HRID 471040 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-26fb8fad8c7d459396052a25a85a995e
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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