Water → 2-Methyl-2-(methylsulfonyl)butanamide

HRID 533545Notes

Reaction equation

HRID 533545 reaction equation
[CH3:1][C:2]([S:30]([CH3:33])(=[O:32])=[O:31])([CH2:13][CH2:14]C1C=CC(B2OC(C)(C)C(C)(C)O2)=CC=1)[C:3]([NH:5]OC1CCCCO1)=[O:4].BrC1C=CC(C2ON=C(CO)C=2)=CC=1.[F-].[Cs+].O>C(OCC)(=O)C.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.O1CCOCC1>[CH3:1][C:2]([S:30]([CH3:33])(=[O:31])=[O:32])([CH2:13][CH3:14])[C:3]([NH2:5])=[O:4]

Participants

8

Reactant 4

HCID 962WaterHCID 25953Cesium fluorideHCID 16641471(5-(4-Bromophenyl)-3-isoxazolyl)methanolHCID 764453942-methanesulfonyl-2-methyl-N-(tetrahydro-pyran-2-yloxy)-4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-butyramide

Product 1

HCID 866687702-Methyl-2-(methylsulfonyl)butanamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

To flask containing 2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]butanamide, which may be prepared as in Preparation 3, (100 mg, 0.208 mmol) was added [5-(4-Bromo-phenyl)-isoxazol-3-yl]-methanol (58.2 mg, 0.229 mmol), cesium fluoride (126 mg, 0.832 mmol), water (200 uL) and 1,4-dioxane (2 mL). To this mixture was added Palladium tetrakis (35.8 mg, 0.031 mmol) and the mixture was heated to 115° C. with stirring for 3 hours. The mixture was diluted with ethyl acetate and washed with aqueous HCl (0.1 N). The phases were separated and the crude organic extract was concentrated to dryness. The crude material was purified via silica gel chromatography eluting with ethyl acetate/heptanes to afford N-hydroxy-4-{4′-[3-hhydroxymethyl)isoxazol-5-yl]biphenyl-4-yl}-2-methyl-2-(methylsulfonyl)butanamide as a solid 21 mg.

Workup

  1. custommay be prepared as in Preparation 3, (100 mg, 0.208 mmol)
  2. washwashed with aqueous HCl (0.1 N)
  3. customThe phases were separated
  4. extractionthe crude organic extract
  5. concentrationwas concentrated to dryness
  6. customThe crude material was purified via silica gel chromatography
  7. washeluting with ethyl acetate/heptanes

Sources & evidence

ORD record
ord-69c2eab377e44ec1a247a2b89246fcb7
Source dataset
uspto-grants-2014_10
Patent number
US08853258B2

Reaction notes

Loading…