Water → 7-(1-Pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro[4.5]decane

HRID 1196508Notes

Reaction equation

HRID 1196508 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][NH:8][CH:7]([C:11]([N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)=O)[CH2:6]2)[O:4][CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>O1CCCC1.C(Cl)(Cl)Cl>[N:13]1([CH2:11][CH:7]2[NH:8][CH2:9][CH2:10][C:5]3([O:1][CH2:2][CH2:3][O:4]3)[CH2:6]2)[CH2:17][CH2:16][CH2:15][CH2:14]1

Participants

7

Reactant 4

HCID 962Water2×HCID 14798Sodium HydroxideHCID 151232461-[(1,4-Dioxa-8-azaspiro[4.5]dec-7-yl)carbonyl]pyrrolidineHCID 21226445Aluminium lithium hydride

Product 1

HCID 151232477-(1-Pyrrolidinylmethyl)-1,4-dioxa-8-azaspiro[4.5]decaneYield 42.8%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of the product of stage (v) (712 mg) in dry tetrahydrofuran (7.5 ml) was added dropwise to a stirred suspension of lithium aluminium hydride (total of 363 mg) in dry tetrahydrofuran (15 ml) under nitrogen. The mixture was heated under reflux for 19 h, allowed to cool for 1 h and water (5 ml) was cautiously added dropwise. More water (10 ml) and aqueous sodium hydroxide (2N, 5 ml) were then added followed by chloroform (25 ml). The insoluble material was filtered off, washed thoroughly with chloroform and the filtrate layers separated. The aqueous layer was re-extracted with chloroform (2×25 ml) and the combined organic solution dried and evaporated to give crude title compound (750 mg) as an oil. This oil was purified by column chromatography on neutral activity I alumina (Type UGl, 22.5 g) eluting with ether-methanol (19:1) to give the title compound as an oil (287 mg). T.l.c. Alumina/ether-methanol (19:1) Rf 0.30.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 19 h
  3. temperatureto cool for 1 h
  4. filtrationThe insoluble material was filtered off
  5. washwashed thoroughly with chloroform
  6. customthe filtrate layers separated
  7. extractionThe aqueous layer was re-extracted with chloroform (2×25 ml)
  8. customthe combined organic solution dried
  9. customevaporated
  10. customto give crude title compound (750 mg) as an oil
  11. customThis oil was purified by column chromatography on neutral activity I alumina (Type UGl, 22.5 g)
  12. washeluting with ether-methanol (19:1)

Sources & evidence

ORD record
ord-91f7525c7ab24db8bc08263f7bfb136e
Source dataset
uspto-grants-1992_05
Patent number
US05114945

Reaction notes

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