2,6-Dimethylmorpholine, cis- → cis-4-[2-(4,4-Dimethylcyclohexyl)-4-(2,6-dimethylmorpholin-4-yl)phenyl]piperazine-1-carboxylic acid t-butyl ester

HRID 32178

반응식

HRID 32178 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][C:15]=2[CH:21]2[CH2:26][CH2:25][C:24]([CH3:28])([CH3:27])[CH2:23][CH2:22]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:29][C@H:30]1[O:35][C@@H:34]([CH3:36])[CH2:33][NH:32][CH2:31]1.CC(C)([O-])C.[Na+].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C(C)=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([N:32]3[CH2:31][C@H:30]([CH3:29])[O:35][C@H:34]([CH3:36])[CH2:33]3)=[CH:16][C:15]=2[CH:21]2[CH2:26][CH2:25][C:24]([CH3:28])([CH3:27])[CH2:23][CH2:22]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 6415002,6-Dimethylmorpholine, cis-HCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 23676156Sodium t-butoxideHCID 597694184-[4-Bromo-2-(4,4-dimethylcyclohexyl)phenyl]piperazine-1-carboxylic acid t-butyl ester

생성물 1

HCID 59769395cis-4-[2-(4,4-Dimethylcyclohexyl)-4-(2,6-dimethylmorpholin-4-yl)phenyl]piperazine-1-carboxylic acid t-butyl ester수율 86.1%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 7237O-Xylene용매

반응 조건

온도
100 °C

실험 절차

A mixture of the 4-[4-bromo-2-(4,4-dimethylcyclohexyl)phenyl]piperazine-1-carboxylic acid t-butyl ester (700 mg, 1.55 mmol) produced in Example (3e), cis-2,6-dimethylmorpholine (268 mg, 2.33 mmol), sodium t-butoxide (372 mg, 3.88 mmol), palladium(II) acetate (35 mg, 0.155 mmol), tri-t-butylphosphonium tetrafluoroborate (135 mg, 0.465 mmol) and xylene (7 mL) was stirred for 2 hours at an external temperature of 100° C. under a nitrogen atmosphere. The reaction mixture was air-cooled to room temperature, and then the insoluble matters were filtered off, water was added to the obtained filtrate and extraction was performed with ethyl acetate. The separated organic layer was washed with water and brine in that order and then dried over anhydrous sodium sulfate. The desiccant was filtered off and the filtrate was concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give 648 mg of the title compound as yellow crystals.

후처리

  1. temperatureThe reaction mixture was air-cooled to room temperature
  2. filtrationthe insoluble matters were filtered off
  3. additionwater was added to the obtained filtrate and extraction
  4. washThe separated organic layer was washed with water and brine in that order
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe desiccant was filtered off
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe resultant residue was purified by silica gel column chromatography (ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-32eb235c33e24e6992c480b63377a8b3
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07425554B2

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