Water → 4-[6-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

HRID 401896

반응식

HRID 401896 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].[CH2:21]([C:25]1[N:26]=[N:27][C:28](Cl)=[CH:29][C:30]=1[C:31]1[CH:36]=[CH:35][C:34]([O:37][CH:38]2[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]2)=[CH:33][CH:32]=1)[CH2:22][CH2:23][CH3:24].O>C1COCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:28]2[N:27]=[N:26][C:25]([CH2:21][CH2:22][CH2:23][CH3:24])=[C:30]([C:31]3[CH:32]=[CH:33][C:34]([O:37][CH:38]4[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]4)=[CH:35][CH:36]=3)[CH:29]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

7

반응물 4

HCID 962WaterHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 866577793-Butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-pyridazine

생성물 1

HCID 673746634-[6-Butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

To a stirred solution of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (94.2 mmol, 18.97 g) in THF (100 mL) at room temperature was added potassium tert-butoxide (87.0 mmol, 9.76 g) and continued stirring for 15 min. The reaction mixture was cooled to 0° C. using an ice bath. To this was added a solution of 3-butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-pyridazine (72.5 mmol, 25.0 g) in THF (100 mL). The reaction mixture was allowed to slowly attain room temperature while stirring overnight. The reaction was poured into a mixture of water (300 mL) and ethyl acetate (300 mL). The mixture was shaken and separated. The aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layer was washed with brine (50 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on 330 g SiO2 cartridge using an ethyl acetate/hexanes gradient to provide 4-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-piperidine-1-carboxylic acid tert-butyl ester.

후처리

  1. customwas allowed to slowly attain room temperature
  2. stirringwhile stirring overnight
  3. stirringThe mixture was shaken
  4. customseparated
  5. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
  6. washThe combined organic layer was washed with brine (50 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified on 330 g SiO2 cartridge

출처 및 근거

ORD 기록
ord-d2baa909299f43b0955afcad52a233bb
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08741900B2

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