Potassium tert-butoxide → 9-Benzyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one

HRID 876051Notes

Reaction equation

HRID 876051 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([CH2:15][NH:16][C:17](=[O:20])[CH2:18]Cl)([OH:14])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+]>O1CCCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2([O:14][CH2:18][C:17](=[O:20])[NH:16][CH2:15]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 52911160N-((1-benzyl-4-hydroxypiperidin-4-yl)methyl)-2-chloroacetamide

Product 1

HCID 205220419-Benzyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-oneYield 62.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of compound 398 (41.9 g, 141 mmol) in tetrahydrofuran (300 mL) was added potassium tert-butoxide (31.8 g, 283 mmol), portionwise over 40 minutes. After 3.5 hours of stirring at room temperature, the reaction was concentrated in vacuo. The residue was diluted with DCM and water, and then neutralized with 3N HCl. The remaining solids were filtered off and the filtrate was concentrated to an oil. The residue was taken up in hot ethanol (100 mL). After allowing the solution to cool to ˜45° C., the salts were filtered off, and the filtrate was concentrated to a brown solid. The crude material was purified by flash chromatography (0-20% methanol in DCM with 1% NH4OH) to give compound 399 as an orange solid (22.8 g, 62%). LCMS-ESI (POS), M/Z, M+1: Found 261.1, Calculated 261.1.

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. additionThe residue was diluted with DCM and water
  3. filtrationThe remaining solids were filtered off
  4. concentrationthe filtrate was concentrated to an oil
  5. temperatureto cool to ˜45° C.
  6. filtrationthe salts were filtered off
  7. concentrationthe filtrate was concentrated to a brown solid
  8. customThe crude material was purified by flash chromatography (0-20% methanol in DCM with 1% NH4OH)

Sources & evidence

ORD record
ord-aa02464064ab4427a2cc5075d0dc0ce6
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Reaction notes

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