Binap, (A+-)- → 1-(4-(Difluoromethoxy)-3-methylphenyl)-3,5-dimethylpiperazine

HRID 1172193ノート

反応式

HRID 1172193 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:9]([F:11])[F:10])=[C:4]([CH3:12])[CH:3]=1.[CH3:13][C@H:14]1[CH2:19][NH:18][CH2:17][C@@H:16]([CH3:20])[NH:15]1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[K+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:10][CH:9]([F:11])[O:8][C:5]1[CH:6]=[CH:7][C:2]([N:18]2[CH2:17][CH:16]([CH3:20])[NH:15][CH:14]([CH3:13])[CH2:19]2)=[CH:3][C:4]=1[CH3:12]

参加物

7

反応物 4

HCID 634876Binap, (A+-)-HCID 6950261rel-(2R,6S)-2,6-dimethylpiperazineHCID 23665647Potassium tert-butoxideHCID 451587104-Bromo-1-(difluoromethoxy)-2-methylbenzene

生成物 1

HCID 670458071-(4-(Difluoromethoxy)-3-methylphenyl)-3,5-dimethylpiperazine収率 41%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

反応条件

温度
80 °C

実験手順

To 4-bromo-1-(difluoromethoxy)-2-methylbenzene (2.36 g, 10.00 mmol) in toluene (50 mL) was added cis-2,6-dimethylpiperazine (5 g, 58.14 mmol), Pd(OAc)2 (120 mg, 0.53 mmol), BINAP (380 mg, 0.61 mmol), and t-BuOK (2.2 g, 19.64 mmol). The resulting solution was stirred for 4 hours at 80° C. The solution was cooled to room temperature and washed with H2O (2×50 mL), dried over Na2SO4, concentrated, and purified by silica gel column chromatography (10:1 CH2Cl2/MeOH) to give 1.1 g (41%) of 1-(4-(difluoromethoxy)-3-methylphenyl)-3,5-dimethylpiperazine.

後処理

  1. temperatureThe solution was cooled to room temperature
  2. washwashed with H2O (2×50 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. custompurified by silica gel column chromatography (10:1 CH2Cl2/MeOH)

出典と根拠

ORDレコード
ord-26c0cb512bcd4776977bed61c94bebad
出典データセット
uspto-grants-2010_11
特許番号
US07834004B2

反応ノート

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