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

HRID 75126Notes

Reaction equation

HRID 75126 reaction equation
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]

Participants

7

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-932d4f52181944358f760287c1a84df4
Source dataset
uspto-grants-2014_09
Patent number
US08835419B2

Reaction notes

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