Morpholine → 2-Chloro-5-(morpholin-4-yl)aniline

HRID 1431559ノート

反応式

HRID 1431559 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:9])=[C:6]([CH:8]=1)[NH2:7].C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[NH:78]1[CH2:83][CH2:82][O:81][CH2:80][CH2:79]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[Cl:9][C:5]1[CH:4]=[CH:3][C:2]([N:78]2[CH2:83][CH2:82][O:81][CH2:80][CH2:79]2)=[CH:8][C:6]=1[NH2:7]

参加物

9

反応物 5

HCID 8083MorpholineHCID 2733832Lithium HexamethyldisilazideHCID 38307312-Chloro-5-bromoanilineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

生成物 1

HCID 176073522-Chloro-5-(morpholin-4-yl)aniline

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
60 °C

実験手順

A mixture of 5-bromo-2-chloroaniline (1.09 g, 5.29 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl, (X-Phos) (202 mg, 0.42 mmol), tris(dibenzylideneacetone)dipalladium (0) (198 mg, 0.22 mmol), and morpholine (2.3 mL, 26.4 mmol) in dry THF (12 mL) was degassed by nitrogen. To this mixture was added lithium bis(trimethylsilyl)amide, 1.0M in THF (25.0 mL, 25.0 mmol) dropwise, and the resulting reaction was heated to 60° C. After 2.5 h, the reaction was cooled to rt then poured into water. After extracting twice with EtOAc and twice with DCM, the combined organic layers were dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on silica gel (0-45% EtOAc in hexanes) to yield 2-chloro-5-morpholinoaniline. 1H NMR (400 MHz, CDCl3) δ ppm 7.12 (1H, d, J=8.6 Hz), 6.42 (2H, m), 4.00 (2H, br. s.), 3.93 (4H, m), 3.22 (4H, m).

後処理

  1. customwas degassed by nitrogen
  2. customthe resulting reaction
  3. temperaturethe reaction was cooled to rt
  4. extractionAfter extracting twice with EtOAc and twice with DCM
  5. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  6. filtrationAfter filtration and concentration
  7. customthe residue was purified on silica gel (0-45% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-4113f4af20ca4ab0bd221b5e39b835fa
出典データセット
uspto-grants-2015_01
特許番号
US08940724B2

反応ノート

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