Water → (+/-)-2-Methyl-2-(methylsulfonyl)-4-(4'-nitrobiphenyl-4-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 533535Notes

Reaction equation

HRID 533535 reaction equation
O.Br[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11]([CH3:26])([S:22]([CH3:25])(=[O:24])=[O:23])[C:12]([NH:14][O:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)=[O:13])=[CH:5][CH:4]=1.[N+:27]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)([O-:29])=[O:28].[F-].[Cs+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:26][C:11]([S:22]([CH3:25])(=[O:24])=[O:23])([CH2:10][CH2:9][C:6]1[CH:7]=[CH:8][C:3]([C:33]2[CH:34]=[CH:35][C:30]([N+:27]([O-:29])=[O:28])=[CH:31][CH:32]=2)=[CH:4][CH:5]=1)[C:12]([NH:14][O:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][O:17]1)=[O:13]

Participants

7

Reactant 4

HCID 962WaterHCID 25953Cesium fluorideHCID 27735524-Nitrophenylboronic acidHCID 76445393(+/-)-4-(4-Bromophenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Product 1

HCID 86668765(+/-)-2-Methyl-2-(methylsulfonyl)-4-(4'-nitrobiphenyl-4-yl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideYield 182.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

Water (1.0 mL) was added to a solution of (+/−)-4-(4-bromophenyl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (0.35 g, 0.806 mmol), which may be prepared as in Preparation 2, Step 4, in 1,4-dioxane (5.0 mL). (4-nitrophenyl)boronic acid (209 mg, 1.01 mmol), cesium fluoride (0.49 mg, 3.22 mmol) and tetrakis(triphenylphosphine)palladium (0.094 g, 0.810 mmol) were added and the solution was heated to 90° C. After 4 hours the reaction was concentrated in vacuo and the resulting residue was triturated with ethyl acetate. The suspension was filtered through celite. The filtrate was washed with brine, dried (Na2SO4), and concentrated in vacuo. Purification on Biotage flash 40S (hexanes/ethyl 6:4-1:1) afforded the title compound as a yellow solid (700 mg, 50%). LCMS m/z 475.2 (M−1).

Workup

  1. concentrationAfter 4 hours the reaction was concentrated in vacuo
  2. customthe resulting residue was triturated with ethyl acetate
  3. filtrationThe suspension was filtered through celite
  4. washThe filtrate was washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customPurification on Biotage flash 40S (hexanes/ethyl 6:4-1:1)

Sources & evidence

ORD record
ord-75e98eee4c114efd9cc16581e75ed24f
Source dataset
uspto-grants-2014_10
Patent number
US08853258B2

Reaction notes

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