2,6-Di-tert-butyl-4-methylphenol → HCID 86699738, compound

HRID 515169Notes

Reaction equation

HRID 515169 reaction equation
ClC1C=CC([N:8]([CH3:32])[C:9]([C:11]2[C:16]([CH3:17])=[CH:15][C:14]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[CH:13][C:12]=2OS(C(F)(F)F)(=O)=O)=[O:10])=CC=1.C([C:37]1[CH:42]=[C:41](C)[CH:40]=[C:39](C(C)(C)C)[C:38]=1O)(C)(C)C.[Cl-:49].[Li+].C([Sn](CCCC)(CCCC)[C:56]1[CH2:60][CH2:59][CH2:58][CH:57]=1)CCC>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:49][C:37]1[CH:38]=[CH:39][C:40]([CH2:32][NH:8][C:9](=[O:10])[C:11]2[C:16]([CH3:17])=[CH:15][C:14]([N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)=[CH:13][C:12]=2[C:56]2[CH2:60][CH2:59][CH2:58][CH:57]=2)=[CH:41][CH:42]=1

Participants

8

Reactant 4

HCID 314042,6-Di-tert-butyl-4-methylphenolHCID 433294Lithium ChlorideHCID 10915290Stannane, tributyl-1-cyclopenten-1-yl-HCID 86699736HCID 86699736, compound

Product 1

HCID 86699738HCID 86699738, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of trifluoro-methanesulfonic acid [2-[(4-chlorophenyl)-methyl-carbamoyl]-3-methyl-5-morpholin-4-yl-phenyl]ester (synthesized according to the method described in section a) of example 12) (1.0 g, 2.03 mmol) in dioxane (50 ml) are added 2,6-di-tert-butyl-4-methylphenol (0.044 g, 0.20 mmol), lithium chloride (0.688 g, 16.3 mmol) and tributyl-1-cyclopenten-1-yl-stannane (1.46 g, 4.06 mmol). The mixture is degassed and flushed with argon for 30 min followed by the addition bis(triphenylphosphine)palladiumchloride (0.17 g, 0.24 mmol). The resulting mixture is heated at 120° C. for 16 h. The reaction mixture is diluted with water (30 ml) and extracted with ethyl acetate (3×50 ml). The organic layer is washed with water (20 ml), saturated potassium fluoride solution (2×20 ml), brine (20 ml) and dried over anhydrous sodium sulfate. Evaporation under vacuum afforded the crude product, which is purified by column chromatography (silica gel-10% KF, 20% ethyl acetate/hexane) to yield N-[(4-chlorophenyl)-methyl]-2-cyclopenten-1-yl-6-methyl-4-morpholin-4-yl-benzamide (0.50 g, 1.22 mmol, 60%).

Workup

  1. customsynthesized
  2. customThe mixture is degassed
  3. customflushed with argon for 30 min
  4. extractionextracted with ethyl acetate (3×50 ml)
  5. washThe organic layer is washed with water (20 ml), saturated potassium fluoride solution (2×20 ml), brine (20 ml)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customEvaporation under vacuum
  8. customafforded the crude product, which
  9. customis purified by column chromatography (silica gel-10% KF, 20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-e982edd4689e4216917dd9d38df770fc
Source dataset
uspto-grants-2015_08
Patent number
US09108936B2

Reaction notes

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