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

HRID 533522Notes

Reaction equation

HRID 533522 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]([F: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>[F:26][C:4]1[CH:3]=[C:2]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:7]=[CH:6][C:5]=1[CH2:8][CH2:9][C:10]([CH3:25])([S:21]([CH3:24])(=[O:23])=[O:22])[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 866687574-(4-Bromo-2-fluorophenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Product 1

HCID 866687584-(3-Fluorobiphenyl-4-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

4-(4-Bromo-2-fluorophenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (250 mg, 0.558 mmol), phenyl boronic acid (91 mg, 0.747 mmol), sodium carbonate (216 mg, 2.04 mmol), and 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 4 N HCl in water and extracted with ethyl acetate (3×15 mL). The organics were combined, dried over magnesium sulfate, filtered and concentrated in vacuo to afford the title compound as a crude brown solid (206.7 mg, 67%). LC-MS m/z 448.3 (M−1)

Workup

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

Sources & evidence

ORD record
ord-fedd5c43c65d4036bcb438643d8cd5a9
Source dataset
uspto-grants-2014_10
Patent number
US08853258B2

Reaction notes

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