Potassium tert-butoxide → 3-(5-Bromo-4-fluoro-2-methyl-phenyl)-4-hydroxy-8-methoxy-1,8-diazaspiro[4.5]dec-3-en-2-one

HRID 1962376Notes

Reaction equation

HRID 1962376 reaction equation
CO[C:3]([C:5]1([NH:13][C:14](=[O:25])[CH2:15][C:16]2[CH:21]=[C:20]([Br:22])[C:19]([F: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].CC(C)([O-])C.[K+]>CN(C)C=O>[Br:22][C:20]1[C:19]([F:23])=[CH:18][C:17]([CH3:24])=[C:16]([C:15]2[C:14](=[O:25])[NH:13][C:5]3([CH2:10][CH2:9][N:8]([O:11][CH3:12])[CH2:7][CH2:6]3)[C:3]=2[OH:4])[CH:21]=1

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 596145984-[2-(5-Bromo-4-fluoro-2-methyl-phenyl)-acetylamino]-1-methoxy-piperidine-4-carboxylic acid methyl ester

Product 1

HCID 596145973-(5-Bromo-4-fluoro-2-methyl-phenyl)-4-hydroxy-8-methoxy-1,8-diazaspiro[4.5]dec-3-en-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[2-(5-bromo-4-fluoro-2-methyl-phenyl)-acetylamino]-1-methoxy-piperidine-4-carboxylic acid methyl ester (6.0 g) in dimethylformamide (20 ml) at 100° C. was added potassium tert-butoxide (3.23 g) and stirring continued at 100° C. for 10 minutes. The reaction mixture was quenched at room temperature by addition of acetic acid (1.64 ml), diluted with water (20 ml) and extracted with tert-butyl methyl ether (3×). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The residue was triturated with acetonitrile, filtered and dried. Yield: 3.69 g of 3-(5-bromo-4-fluoro-2-methyl-phenyl)-4-hydroxy-8-methoxy-1,8-diaza-spiro[4.5]dec-3-en-2-one (title compound C19) as a solid, mp: 229-230° C.

Workup

  1. customThe reaction mixture was quenched at room temperature by addition of acetic acid (1.64 ml)
  2. additiondiluted with water (20 ml)
  3. extractionextracted with tert-butyl methyl ether (3×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was triturated with acetonitrile
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-efd8fa4acb224f978d0dfd6bff44acba
Source dataset
uspto-grants-2013_04
Patent number
US08415369B2

Reaction notes

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