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

HRID 1473785노트

반응식

HRID 1473785 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-48fea86930424b23aac87bba7b8082fe
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018135B2

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