2-Iodophenol → HCID 86668768, compound

HRID 533543Notes

Reaction equation

HRID 533543 reaction equation
[CH3:1][C:2]([S:30]([CH3:33])(=[O:32])=[O:31])([CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18](B2OC(C)(C)C(C)(C)O2)=[CH:17][CH:16]=1)[C:3]([NH:5][O:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][O:8]1)=[O:4].Br[C:35]1[CH:36]=[CH:37][C:38](=[C:41]2[C:46](=[O:47])OC(C)(C)OC2=O)NC=1.IC1C=CC=CC=1O.[F-].[Cs+]>C(OCC)(=O)C.O.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>[OH:47][C:46]1[CH:35]=[CH:36][CH:37]=[CH:38][C:41]=1[C:18]1[CH:17]=[CH:16][C:15]([CH2:14][CH2:13][C:2]([CH3:1])([S:30]([CH3:33])(=[O:32])=[O:31])[C:3]([NH:5][O:6][CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][O:8]2)=[O:4])=[CH:20][CH:19]=1

Participants

9

Reactant 4

HCID 107842-IodophenolHCID 25953Cesium fluorideHCID 574434985-(5-Bromopyridin-2(1H)-ylidene)-2,2-dimethyl-1,3-dioxane-4,6-dioneHCID 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 86668768HCID 86668768, compound

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
115 °C

Procedure

To a 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 prepared as in Preparation Number 3 (150 mg, 0.312 mmol) was added 2-iodophenol (89.3 mg, 0.406 mmol), cesium fluoride (190 mg, 1.25 mmol), water (500 uL) and 1,4-dioxane (3 mL). To this mixture was added Palladium tetrakis (54.3 mg, 0.047 mmol) and the mixture was heated to 115° C. with stirring overnight. The mixture was diluted with ethyl acetate and water. The phases were separated and the crude organic extract was concentrated in vacuo to dryness. The crude material was purified via silica gel chromatography eluting with ethyl acetate/heptanes to afford 4-(2′-hydroxybiphenyl-4-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide as solid. 19.6 mg LCMS: (M−1) 446.3.

Workup

  1. additionTo a flask containing
  2. customThe phases were separated
  3. extractionthe crude organic extract
  4. concentrationwas concentrated in vacuo to dryness
  5. customThe crude material was purified via silica gel chromatography
  6. washeluting with ethyl acetate/heptanes

Sources & evidence

ORD record
ord-0e2a7591f8aa451d900ec777da5c4044
Source dataset
uspto-grants-2014_10
Patent number
US08853258B2

Reaction notes

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