2,6-Di-tert-butyl-4-methylphenol → HCID 86699735, compound

HRID 515165Notes

Reaction equation

HRID 515165 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(C([Sn])=C(CC[CH2:63][CH3:64])CCCC)CCC>O1CCOCC1>[Cl:49][C:37]1[CH:38]=[CH:39][C:40]([CH2:32][NH:8][C:9](=[O:10])[C:11]2[C:12]([CH:63]=[CH2:64])=[CH:13][C:14]([N:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)=[CH:15][C:16]=2[CH3:17])=[CH:41][CH:42]=1

Participants

6

Reactant 4

HCID 314042,6-Di-tert-butyl-4-methylphenolHCID 433294Lithium ChlorideHCID 53438229Tri(butyl)vinyltinHCID 86699736HCID 86699736, compound

Product 1

HCID 86699735HCID 86699735, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of trifluoro-methanesulfonic acid [2-[(4-chlorophenyl)-methyl-carbamoyl]-3-methyl-5-morpholin-4-yl-phenyl]ester (0.20 g, 0.4 mmol) in dioxane (10 ml) are added 2,6-di-tert-butyl-4-methylphenol (few crystals), lithium chloride (0.052 g, 1.22 mmol) and tributylvinyl tin (0.13 ml, 0.45 mmol). The mixture is degassed and flushed with argon for 30 min followed by the addition of tetrakis(triphenylphosphin)palladium(0) (0.01 g, 0.008 mmol). The resulting mixture is heated at 110° C. for 16 h. The reaction mixture is concentrated, diluted with water (10 ml) and extracted with ethyl acetate (3×30 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, 30% ethyl acetate/hexane) to yield N-[(4-chlorophenyl)-methyl]-2-methyl-4-morpholin-4-yl-6-vinyl-benzamide (0.12 g, 0.32 mmol, 79%).

Workup

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

Sources & evidence

ORD record
ord-f91b9625a71d4ba884dff48609577e09
Source dataset
uspto-grants-2015_08
Patent number
US09108936B2

Reaction notes

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