Tri-tert-butylphosphine tetrafluoroborate → (S)-4-[2-(4,4-Diethylcyclohexyl)-4-(3-methoxypiperidin-1-yl)phenyl]piperazine-1-carboxylic acid t-butyl ester

HRID 32162

반응식

HRID 32162 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]([CH2:29][CH3:30])([CH2:27][CH3:28])[CH2:23][CH2:22]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:32][O:33][C@H:34]1[CH2:39][CH2:38][CH2:37][NH:36][CH2:35]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:36]3[CH2:37][CH2:38][CH2:39][C@H:34]([O:33][CH3:32])[CH2:35]3)=[CH:16][C:15]=2[CH:21]2[CH2:26][CH2:25][C:24]([CH2:29][CH3:30])([CH2:27][CH3:28])[CH2:23][CH2:22]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 2734635Tri-tert-butylphosphine tetrafluoroborate2회HCID 23676156Sodium t-butoxide2회HCID 597694214-[4-Bromo-2-(4,4-diethylcyclohexyl)phenyl]piperazine-1-carboxylic acid t-butyl esterHCID 67332844(3S)-3-methoxypiperidine hydrochloride

생성물 1

HCID 59769434(S)-4-[2-(4,4-Diethylcyclohexyl)-4-(3-methoxypiperidin-1-yl)phenyl]piperazine-1-carboxylic acid t-butyl ester수율 35.9%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매2회HCID 7237O-Xylene용매

반응 조건

온도
100 °C

실험 절차

A mixture of 4-[4-bromo-2-(4,4-diethylcyclohexyl)phenyl]piperazine-1-carboxylic acid t-butyl ester (153 mg, 0.32 mmol) produced in Example (38c), (S)-3-methoxypiperidine hydrochloride (72.8 mg, 0.48 mmol) produced in Example (50a), sodium t-butoxide (200 mg, 2.08 mmol), palladium(II) acetate (14.4 mg, 0.064 mmol), tri-t-butylphosphonium tetrafluoroborate (57.7 mg, 0.192 mmol) and xylene (4 mL) was stirred for 6 hours and 10 minutes at an external temperature of 100° C. under a nitrogen atmosphere. To the reaction mixture were further added sodium t-butoxide (100 mg, 1.04 mmol), palladium(II) acetate (7.2 mg, 0.032 mmol) and tri-t-butylphosphonium tetrafluoroborate (27.9 mg, 0.096 mmol), followed by stirring for 1 hour at an external temperature of 100° C. under a nitrogen atmosphere. The reaction mixture was air-cooled to room temperature and then purified by NH silica gel column chromatography (ethyl acetate/hexane) to give 59 mg of the title compound as a brown oil.

후처리

  1. stirringby stirring for 1 hour at an external temperature of 100° C. under a nitrogen atmosphere
  2. temperatureThe reaction mixture was air-cooled to room temperature
  3. custompurified by NH silica gel column chromatography (ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-08cae7ba9d5d4821836adb264af0ab90
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07425554B2

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