Sodium Bicarbonate → 4-{[2-(4-Chloro-2,6-dimethyl-phenyl)-acetyl]-hydroxy-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester

HRID 1473785Notes

Reaction equation

HRID 1473785 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10](Cl)=[O:11])=[C:4]([CH3:13])[CH:3]=1.C(=O)([O-])O.[Na+].[CH3:19][O:20][C:21]([C:23]1([NH:31][OH:32])[CH2:28][CH2:27][N:26]([O:29][CH3:30])[CH2:25][CH2:24]1)=[O:22]>C1COCC1>[CH3:19][O:20][C:21]([C:23]1([N:31]([C:10](=[O:11])[CH2:9][C:5]2[C:6]([CH3:8])=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=2[CH3:13])[OH:32])[CH2:28][CH2:27][N:26]([O:29][CH3:30])[CH2:25][CH2:24]1)=[O:22]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 11746058(4-Chloro-2,6-dimethyl-phenyl)-acetyl chlorideHCID 866574654-Hydroxyamino-1-methoxy-piperidine-4-carboxylic acid methyl ester

Product 1

HCID 584280914-{[2-(4-Chloro-2,6-dimethyl-phenyl)-acetyl]-hydroxy-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (4-chloro-2,6-dimethyl-phenyl)-acetyl chloride (2.90 g, 13.4 mmol) in THF (25 ml) was added sodium hydrogen carbonate (1.90 g, 22.7 mmol) at 0° C., followed by 4-hydroxyamino-1-methoxy-piperidine-4-carboxylic acid methyl ester (preparation example 11, step 3; compound P4ii.2) (2.73 g, 13.4 mmol) dissolved in THF (25 ml) dropwise. The reaction mixture was stirred at 0° C. for 30 minutes, then further 30 minutes at room temperature. After completion of the reaction indicated by TLC and LC/MS, the reaction mixture was filtered and the residue (NaCl) washed with THF. The filtrate was concentrated to dryness and stirred several times with little amounts of an ether/hexane mixture (1:1) to remove side products. Finally, the compound was washed with ether to yield pure 4-{[2-(4-chloro-2,6-dimethyl-phenyl)-acetyl]-hydroxy-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester (compound P3ii.34) as white solid. Yield: 3.7 g, mp 228-231° C.

Workup

  1. customfurther 30 minutes
  2. customat room temperature
  3. filtrationthe reaction mixture was filtered
  4. washthe residue (NaCl) washed with THF
  5. concentrationThe filtrate was concentrated to dryness
  6. stirringstirred several times with little amounts of an ether/hexane mixture (1:1)
  7. customto remove side products
  8. washFinally, the compound was washed with ether

Sources & evidence

ORD record
ord-48fea86930424b23aac87bba7b8082fe
Source dataset
uspto-grants-2015_04
Patent number
US09018135B2

Reaction notes

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