Hydrochloric Acid → 4-Hydroxy-8-methoxy-1-prop-2-ynyloxy-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-2-one

HRID 1473773Notes

Reaction equation

HRID 1473773 reaction equation
C[O:2][C:3]([C:5]1([N:13]([O:26][CH2:27][C:28]#[CH:29])[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.C[O-].[Na+].Cl.[Cl-].[Na+]>CN(C)C=O>[OH:2][C:3]1[C:5]2([CH2:10][CH2:9][N:8]([O:11][CH3:12])[CH2:7][CH2:6]2)[N:13]([O:26][CH2:27][C:28]#[CH:29])[C:14](=[O:25])[C:15]=1[C:16]1[C:17]([CH3:24])=[CH:18][C:19]([CH3:23])=[CH:20][C:21]=1[CH3:22]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 5234Sodium ChlorideHCID 10942334Sodium MethoxideHCID 584280801-Methoxy-4-{prop-2-ynyloxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester

Product 1

HCID 584279664-Hydroxy-8-methoxy-1-prop-2-ynyloxy-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-{prop-2-ynyloxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester (150 mg, 0.41 mmol) in dimethylformamide (2 ml) at 0° C. was added sodium methoxide (33 mg, 0.62 mmol) in one portion and stirring continued at room temperature for 4 hours. The reaction mixture was poured on ice water, acidified to pH 5-6 with an aqueous HCl solution, saturated with sodium chloride and thoroughly extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (ethyl acetate/hexane 2:1). Yield: 14 mg of 4-hydroxy-8-methoxy-1-prop-2-ynyloxy-3-(2,4,6-trimethyl-phenyl)-1,8-diaza-spiro[4.5]dec-3-en-2-one (title compound P2ii.8) as a tan solid.

Workup

  1. additionThe reaction mixture was poured on ice water
  2. extractionthoroughly extracted with ethyl acetate
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel (ethyl acetate/hexane 2:1)

Sources & evidence

ORD record
ord-510ae14274d742dfaa7b9be86174026a
Source dataset
uspto-grants-2015_04
Patent number
US09018135B2

Reaction notes

Loading…