Hydrochloric Acid → 3-(4-Chloro-2,6-dimethyl-phenyl)-1,4-dihydroxy-8-methoxy-1,8-diaza-spiro[4.5]dec-3-en-2-one

HRID 1473786Notes

Reaction equation

HRID 1473786 reaction equation
C[O:2][C:3]([C:5]1([N:13]([C:15](=[O:26])[CH2:16][C:17]2[C:22]([CH3:23])=[CH:21][C:20]([Cl:24])=[CH:19][C:18]=2[CH3:25])[OH:14])[CH2:10][CH2:9][N:8]([O:11][CH3:12])[CH2:7][CH2:6]1)=O.CC(C)([O-])C.[K+].O.Cl>CN(C)C=O>[Cl:24][C:20]1[CH:19]=[C:18]([CH3:25])[C:17]([C:16]2[C:15](=[O:26])[N:13]([OH:14])[C:5]3([CH2:6][CH2:7][N:8]([O:11][CH3:12])[CH2:9][CH2:10]3)[C:3]=2[OH:2])=[C:22]([CH3:23])[CH:21]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 23665647Potassium tert-butoxideHCID 584280914-{[2-(4-Chloro-2,6-dimethyl-phenyl)-acetyl]-hydroxy-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester

Product 1

HCID 584279803-(4-Chloro-2,6-dimethyl-phenyl)-1,4-dihydroxy-8-methoxy-1,8-diaza-spiro[4.5]dec-3-en-2-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 4-{[2-(4-chloro-2,6-dimethyl-phenyl)-acetyl]-hydroxy-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester (0.40 g, 1.04 mmol) in dimethylformamide (3 ml) at 0° C. was added potassium tert-butoxide (0.35 g, 3.12 mmol) in portions. After completion of the addition, stirring was continued at 0° C. for 30 minutes and at room temperature overnight. The reaction mixture was poured into cold water (0° C.), the pH adjusted to ca 5.5 by adding 1 N HCl and then thoroughly extracted with ethyl acetate (three times). The combined organic layers were washed with water and brine, dried over sodium sulfate and concentrated. The resulting crude material was purified by column chromatography on silica gel (gradient ethyl acetate/cyclohexane 1:1→ethyl acetate). Yield: 0.14 g of 3-(4-chloro-2,6-dimethyl-phenyl)-1,4-dihydroxy-8-methoxy-1,8-diaza-spiro[4.5]dec-3-en-2-one (compound P2ii.103) as a white solid.

Workup

  1. additionAfter completion of the addition
  2. extractionthoroughly extracted with ethyl acetate (three times)
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe resulting crude material was purified by column chromatography on silica gel (gradient ethyl acetate/cyclohexane 1:1→ethyl acetate)

Sources & evidence

ORD record
ord-c18f0769a7194aa1b04a2708d9725e87
Source dataset
uspto-grants-2015_04
Patent number
US09018135B2

Reaction notes

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