Ammonium Chloride → 4-Hydroxy-8-methoxy-1-(tetrahydro-furan-2-yloxy)-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-2-one

HRID 1473781Notes

Reaction equation

HRID 1473781 reaction equation
CO[C:3]([C:5]1([N:13]([O:26][CH:27]2[CH2:31][CH2:30][CH2:29][O:28]2)[C:14](=[O:25])[CH2:15][C:16]2[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][C:17]=2[CH3:24])[CH2:10][CH2:9][N:8]([O:11][CH3:12])[CH2:7][CH2:6]1)=[O:4].C[O-].[Na+].[Cl-].[NH4+]>CN(C)C=O>[OH:4][C:3]1[C:5]2([CH2:6][CH2:7][N:8]([O:11][CH3:12])[CH2:9][CH2:10]2)[N:13]([O:26][CH:27]2[CH2:31][CH2:30][CH2:29][O:28]2)[C:14](=[O:25])[C:15]=1[C:16]1[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][C:17]=1[CH3:24]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 10942334Sodium MethoxideHCID 584280531-Methoxy-4-{(tetrahydro-furan-2-yloxy)-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester

Product 1

HCID 584280204-Hydroxy-8-methoxy-1-(tetrahydro-furan-2-yloxy)-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-methoxy-4-{(tetrahydro-furan-2-yloxy)-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester (70 g, 161.1 mmol) in dimethylformamide (350 ml) at 10° C. was added sodium methoxide (26.9 g, 483.3 mmol) in four portions and stirring continued at 10° C. for 30 minutes, then at room temperature for 2 hours. The reaction mixture was poured on cold saturated aqueous ammonium chloride and thoroughly extracted with ethyl acetate (6×100 ml). The combined organic layers were washed with brine, dried over sodium sulfate, concentrated and dried in vacuo. The residue was triturated with hexane, filtered and the solid dried. Yield: 51.0 g of 4-hydroxy-8-methoxy-1-(tetrahydro-furan-2-yloxy)-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-2-one (title compound P2ii.18) as a tan solid, mp 144-146° C.

Workup

  1. waitat room temperature for 2 hours
  2. extractionthoroughly extracted with ethyl acetate (6×100 ml)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customdried in vacuo
  7. customThe residue was triturated with hexane
  8. filtrationfiltered
  9. customthe solid dried

Sources & evidence

ORD record
ord-ed581916c85b42d891e8edc38a986ea0
Source dataset
uspto-grants-2015_04
Patent number
US09018135B2

Reaction notes

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