Dimethyl Sulfoxide → 5-Benzyl-1-oxa-5-azaspiro[2.5]octane

HRID 1593111Notes

Reaction equation

HRID 1593111 reaction equation
[H-].[Na+].[CH2:3]([N:10]1[CH2:15][CH2:14][CH2:13][C:12](=[O:16])[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:17]S(C)=O>C1COCC1>[CH2:3]([N:10]1[CH2:15][CH2:14][CH2:13][C:12]2([O:16][CH2:17]2)[CH2:11]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 679Dimethyl Sulfoxide2×HCID 24758Sodium hydrideHCID 966503-Piperidinone, 1-(phenylmethyl)-

Product 1

HCID 137207665-Benzyl-1-oxa-5-azaspiro[2.5]octaneYield 71%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (583 mg, 14.6 mmol) in DMSO (6 mL) was heated to 55 C. for 1 h. The reaction mixture is cooled to 0 C. and Me3SI (3 g, 14.62 mmol) dissolved in THF (9.8 mL) was added dropwise. 1-Benzyl-piperidine-3-one (1.5 g, 6.64 mmol) dissolved in DMSO (10 mL) was added 15 minutes later. After completion of addition the reaction proceded at RT. After 30 min. the reaction was quenched with water. The aqueous layer was extracted with hexanes. Combined organic layers were dried over Na2SO4 and concentrated. The crude material was purified using silica gel chromatography (9:1 DCM:hexanes in 2 M ammonia in EtOH) to yield 5-benzyl-1-oxa-5-aza-spiro[2.5]octane (960 mg, 71%). MH+ (204).

Workup

  1. temperatureThe reaction mixture is cooled to 0 C
  2. additionwas added dropwise
  3. additionwas added 15 minutes later
  4. additionAfter completion of addition the reaction
  5. customproceded at RT
  6. customAfter 30 min. the reaction was quenched with water
  7. extractionThe aqueous layer was extracted with hexanes
  8. dry with materialCombined organic layers were dried over Na2SO4
  9. concentrationconcentrated
  10. customThe crude material was purified

Sources & evidence

ORD record
ord-42d5a53f51df4fa4be83f4ef92b57cbb
Source dataset
uspto-grants-2007_11
Patent number
US07294637B2

Reaction notes

Loading…