Water → (R)-2-{2-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

HRID 2168639

반응식

HRID 2168639 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:14][CH2:15][OH:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH2:19]([C:23]1[N:24]=[N:25][C:26](Cl)=[CH:27][C:28]=1[C:29]1[CH:34]=[CH:33][C:32]([O:35][CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)=[CH:31][CH:30]=1)[CH2:20][CH2:21][CH3:22].O>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:14][CH2:15][O:16][C:26]1[N:25]=[N:24][C:23]([CH2:19][CH2:20][CH2:21][CH3:22])=[C:28]([C:29]2[CH:30]=[CH:31][C:32]([O:35][CH:36]3[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]3)=[CH:33][CH:34]=2)[CH:27]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 962WaterHCID 24758Sodium hydrideHCID 15142441,1-Dimethylethyl (2R)-2-(2-hydroxyethyl)-1-piperidinecarboxylateHCID 866577793-Butyl-6-chloro-4-(4-cyclohexyloxy-phenyl)-pyridazine

생성물 1

HCID 67375014(R)-2-{2-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

To a stirred solution of (R)-2-(2-hydroxy-ethyl)-piperidine-1-carboxylic acid tert-butyl ester (0.87 mmol, 0.20 g) in DMF (1.0 mL) at room temperature was added sodium hydride (60% dispersion in mineral oil) (2.61 mmol, 0.104 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 (Example 14, 0.435 mmol, 0.15 g) in DMF (1.0 mL). After completion of addition, the reaction mixture was warmed to 50° C. for 12 hour. The reaction was poured into a mixture of water (10 mL) and ethyl acetate (5 mL). The mixture was shaken and separated. The ethyl acetate layer was washed with brine (2 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on a 12 g SiO2 cartridge using ethyl acetate/hexanes gradient to give (R)-2-{2-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxy]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester.

후처리

  1. additionAfter completion of addition
  2. temperaturethe reaction mixture was warmed to 50° C. for 12 hour
  3. stirringThe mixture was shaken
  4. customseparated
  5. washThe ethyl acetate layer was washed with brine (2 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified on a 12 g SiO2 cartridge

출처 및 근거

ORD 기록
ord-c26f3a7d0c3e42eb80525252085e7760
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045461B2

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