Hydrochloric Acid → 2-Methyl-4-(3-methylbiphenyl-4-yl)-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 533515Notes

Reaction equation

HRID 533515 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([CH3:25])([S:21]([CH3:24])(=[O:23])=[O:22])[C:11]([NH:13][O:14][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][O:16]2)=[O:12])=[C:4]([CH3:26])[CH:3]=1.[C:27]1(B(O)O)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(=O)([O-])[O-].[Na+].[Na+].BrC1C=CC(CCC(C)(S(C)(=O)=O)C(O)=O)=CC=1.Cl>O.O1CCOCC1>[CH3:25][C:10]([S:21]([CH3:24])(=[O:23])=[O:22])([CH2:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:3][C:4]=1[CH3:26])[C:11]([NH:13][O:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][O:16]1)=[O:12]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 66577906(+/-)-4-(4-Bromophenyl)-2-methyl-2-(methylsulfonyl)butanoic acidHCID 866687554-(4-Bromo-2-methylphenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Product 1

HCID 866687562-Methyl-4-(3-methylbiphenyl-4-yl)-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideYield 68.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

4-(4-Bromo-2-methylphenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (250 mg, 0.558 mmol), phenyl boronic acid (102 mg, 0.837 mmol), sodium carbonate (181 mg, 1.71 mmol), Pd (II) EnCat (144 mg, 0.056 mmol, 0.39 mmol/g loading) were combined in a 2-5 mL microwave vial followed by the addition of 2 mL of dioxane, and 2 mL of water. The reaction was irradiated in a microwave at 120° C. for 40 minutes, followed by neutralization through the addition of 5 mL of aqueous 4N HCl and the mixture was extracted with ethyl acetate (3×15 mL). The organics were combined, dried over magnesium sulfate, filtered and concentrated onto silica gel. Silica chromatography (30% ethyl acetate 70% heptane for 10 minutes, then 30% ethyl acetate 70% heptane to 60% ethyl acetate 40% heptane for 40 minutes) afforded the title compound as a white solid (170 mg, 68%). LC-MS m/z 444.2 (M−1)

Workup

  1. customThe reaction was irradiated in a microwave at 120° C. for 40 minutes
  2. extractionthe mixture was extracted with ethyl acetate (3×15 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated onto silica gel

Sources & evidence

ORD record
ord-e80911bc8fb04ba6a1f8afc0f8a3ac19
Source dataset
uspto-grants-2014_10
Patent number
US08853258B2

Reaction notes

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