1,4-Dioxane → HCID 66621877, compound

HRID 416000Notes

Reaction equation

HRID 416000 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]([CH2:6][CH:7]2[CH2:11][CH2:10][N:9]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]3)[C:8]2=[O:18])=[C:4]([O:21][C:22]([F:25])([F:24])[F:23])[CH:3]=1.[CH3:26][O:27][C:28]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)=[O:29].O1CCOCC1.C([O-])(=O)C.[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CS(C)=O>[CH3:26][O:27][C:28]([C:30]1[CH:35]=[CH:34][C:33]([C:2]2[CH:20]=[CH:19][C:5]([CH2:6][CH:7]3[CH2:11][CH2:10][N:9]([CH:12]4[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]4)[C:8]3=[O:18])=[C:4]([O:21][C:22]([F:25])([F:24])[F:23])[CH:3]=2)=[CH:32][CH:31]=1)=[O:29]

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 517044Potassium AcetateHCID 27343694-Methoxycarbonylphenylboronic acidHCID 66622239HCID 66622239, compound

Product 1

HCID 66621877HCID 66621877, compoundYield 90.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

Combine 3-(4-bromo-2-(trifluoromethoxy)benzyl)-1-cyclohexylpyrrolidin-2-one (9.68 g, 23.0 mmol), 4-(methoxycarbonyl)phenylboronic acid (8.29 g, 46.1 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) (2.87 g, 3.9 mmol), dioxane (400 mL) and DMSO (8 mL) in a 1 L flask equipped with a magnetic stir bar, reflux condenser, and N2 inlet. Add potassium acetate (9.04 g, 92.1 mmol) and heat to 80° C. while stirring for 2 hours. Cool to room temperature, filter through silica gel and rinse with ethyl acetate (400 mL). Wash with water (2×400 mL) and saturated sodium chloride solution (1×400 mL), then dry over anhydrous magnesium sulfate and concentrate to an oil. Purify the crude product via silica gel chromatography eluting with 10% to 20% ethyl acetate in hexanes to afford 9.86 g (90%) of the product as a white solid. MS (m/z): 476 (M+1).

Workup

  1. temperaturereflux condenser, and N2 inlet
  2. filtrationfilter through silica gel
  3. washrinse with ethyl acetate (400 mL)
  4. washWash with water (2×400 mL) and saturated sodium chloride solution (1×400 mL)
  5. dry with materialdry over anhydrous magnesium sulfate
  6. concentrationconcentrate to an oil
  7. customPurify the crude product via silica gel chromatography
  8. washeluting with 10% to 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-5df434fb00d348d3ab409fc3631ecc4f
Source dataset
uspto-grants-2012_01
Patent number
US08088776B2

Reaction notes

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