(alphaR)-2,4-Dichloro-alpha-methylbenzenemethanamine → (R)-5-(t-butyldimethylsilyloxy)-2-chloro-N-(1-(2,4-dichlorophenyl)ethyl)aniline

HRID 75126ノート

反応式

HRID 75126 の反応式
Br[C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]=1[Cl:16])[O:5][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[Cl:17][C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=1[C@H:25]([NH2:27])[CH3:26].CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Si:6]([O:5][C:4]1[CH:13]=[CH:14][C:15]([Cl:16])=[C:2]([CH:3]=1)[NH:27][C@@H:25]([C:19]1[CH:20]=[CH:21][C:22]([Cl:24])=[CH:23][C:18]=1[Cl:17])[CH3:26])([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]

参加物

7

反応物 3

HCID 2496565(alphaR)-2,4-Dichloro-alpha-methylbenzenemethanamineHCID 11001786(3-Bromo-4-chlorophenoxy)-t-butyldimethylsilaneHCID 23676156Sodium t-butoxide

生成物 1

HCID 86689039(R)-5-(t-butyldimethylsilyloxy)-2-chloro-N-(1-(2,4-dichlorophenyl)ethyl)aniline収率 92%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 634876Binap, (A+-)-触媒HCID 1140Toluene溶媒

反応条件

温度
110 °C

実験手順

To a mixture of (3-bromo-4-chlorophenoxy)-t-butyldimethylsilane (15.0 g, 46.8 mmol) and (1R)-1-(2,4-dichlorophenyl)ethanamine (9.7 g, 51.5 mmol) in anhydrous toluene (250 mL) were added palladium(II) acetate (Pd(OAc)2) (0.42 g, 1.9 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP) (1.74 g, 2.80 mmol), and sodium t-butoxide (NaO-tBu) (6.3 g, 65.52 mmol). The resulting mixture was heated at 110° C. under nitrogen for 3 h. After cooling to room temperature, the suspension was filtered through a plug of Celite, and washed with ethyl acetate (EtOAc) (100 mL). The filtrate was concentrated in vacuo. The resulting residue was diluted with deionized water, and extracted with ethyl acetate (500 mL). The organic layer was washed with brine, dried (Na2SO4), and concentrated in vacuo. The crude residue was purified by flash chromatography (SiO2, 0-15% ethyl acetate in hexanes) to afford (R)-5-(t-butyldimethylsilyloxy)-2-chloro-N-(1-(2,4-dichlorophenyl)ethyl)aniline as a viscous oil (18.5 g, 42.9 mmol, 92%). 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J=1.6 Hz, 1H), 7.32 (d, J=8.8 Hz, 1H), 7.19 (dd, J=1.6, 8.4 Hz, 1H), 7.08 (d, J=8.4 Hz, 1H), 6.13 (dd, J=2.2, 8.4 Hz, 1H), 5.71 (d, J=2.4 Hz, 1H), 4.87-4.84 (m, 1H), 4.67 (d, J=4.8 Hz, 1H), 1.58 (d, J=6.8 Hz, 3H), 0.98 (s, 9H), 0.02 (s, 3H), 0.01 (s, 3H).

後処理

  1. temperatureAfter cooling to room temperature
  2. filtrationthe suspension was filtered through a plug of Celite
  3. washwashed with ethyl acetate (EtOAc) (100 mL)
  4. concentrationThe filtrate was concentrated in vacuo
  5. additionThe resulting residue was diluted with deionized water
  6. extractionextracted with ethyl acetate (500 mL)
  7. washThe organic layer was washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was purified by flash chromatography (SiO2, 0-15% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-932d4f52181944358f760287c1a84df4
出典データセット
uspto-grants-2014_09
特許番号
US08835419B2

反応ノート

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