O-Xylene → (S)-4-[2-(4,4-Diethylcyclohexyl)-4-(3-methoxypiperidin-1-yl)phenyl]piperazine-1-carboxylic acid t-butyl ester

HRID 2218808

反応式

HRID 2218808 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2C=[CH:18][C:17](Br)=[CH:16][C:15]=2C2CCC(C)(C)CC2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:30][O:31][C@H:32]1[CH2:37][CH2:36][CH2:35][NH:34][CH2:33]1.C[C:39]([CH3:42])([O-])C.[Na+].F[B-](F)(F)F.[C:49]([PH+](C(C)(C)C)C(C)(C)C)(C)(C)[CH3:50].[C:62]1([CH3:69])[C:63](C)=[CH:64][CH:65]=[CH:66][CH:67]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[CH:16][C:17]([N:34]3[CH2:35][CH2:36][CH2:37][C@H:32]([O:31][CH3:30])[CH2:33]3)=[CH:18][C:69]=2[CH:62]2[CH2:67][CH2:66][C:65]([CH2:39][CH3:42])([CH2:49][CH3:50])[CH2:64][CH2:63]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 5

HCID 7237O-XyleneHCID 2734635Tri-tert-butylphosphine tetrafluoroborate2 回HCID 23676156Sodium t-butoxide2 回HCID 597694184-[4-Bromo-2-(4,4-dimethylcyclohexyl)phenyl]piperazine-1-carboxylic acid t-butyl esterHCID 67332844(3S)-3-methoxypiperidine hydrochloride

生成物 1

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

試薬・触媒・溶媒 1

HCID 167845palladium(II) acetate触媒2 回

反応条件

温度
100 °C

実験手順

A mixture of 4-[4-bromo-2-(4,4-dimethylcyclohexyl)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.

後処理

  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)

出典と根拠

ORDレコード
ord-7c09990995574c7ca1fdbdfcdb406765
出典データセット
uspto-grants-2008_08
特許番号
US07410971B2

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