Phenylboronic Acid → N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-(6-phenylpyridin-3-yl)butanamide

HRID 533529Notes

Reaction equation

HRID 533529 reaction equation
C(=O)(O)[O-].[Na+].[C:6]1(B(O)O)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.Br[C:16]1[N:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24]([CH3:33])([S:29]([CH3:32])(=[O:31])=[O:30])[C:25]([NH:27][OH:28])=[O:26])=[CH:18][CH:17]=1.CN(C=O)C.O>Cl.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>[OH:28][NH:27][C:25](=[O:26])[C:24]([CH3:33])([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:23][CH2:22][C:19]1[CH:20]=[N:21][C:16]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 66827Phenylboronic AcidHCID 516892Sodium BicarbonateHCID 21962138N,N-Dimethylformamide--water (1/1)HCID 866687624-(6-Bromopyridin-3-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

Product 1

HCID 51355299N-Hydroxy-2-methyl-2-(methylsulfonyl)-4-(6-phenylpyridin-3-yl)butanamideYield 36.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 313Hydrochloric AcidSolvent

Procedure

A solution of tetrakis(triphenylphosphine)palladium (0) (59 mg, 0.023 mmol, 0.1 equiv), sodium bicarbonate (45 mg, 0.73 mmol, 3.2 equiv), phenylboronic acid (42 mg, 0.35 mmol, 1.5 equiv), and 4-(6-bromopyridin-3-yl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide (81 mg, 0.23 mmol, 1.0 equiv) in 1:1 DMF-water (2 mL) was heated at 130° C. for 1 h. The reaction was diluted with 0.5 M hydrochloric acid (10 mL) and extracted with ethyl acetate (3×10 mL). The organic layers (from the acidic extraction) were discarded. The aqueous phase was basified (to pH=8) with a saturated aqueous sodium bicarbonate solution and then extracted with ethyl acetate (3×15 mL). The combined organic layers (from the second basic extraction) were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel (1:0-9:1 dichloromethane/methanol) to provide the title compound (29 mg, 36%). LCMS m/z 349.2 (M+1). 1H NMR (400 MHz, CD3OD) δ 1.69 (s, 3H), 2.13 (m, 1H), 2.55-2.65 (m, 2H), 2.83 (m, 1H), 3.06 (s, 3H), 7.40-7.50 (m, 3H), 7.78-7.83 (m, 2H), 7.89-7.92 (m, 2H), 8.50 (br s, 1H).

Workup

  1. extractionextracted with ethyl acetate (3×10 mL)
  2. extractionThe organic layers (from the acidic extraction)
  3. extractionextracted with ethyl acetate (3×15 mL)
  4. extractionThe combined organic layers (from the second basic extraction)
  5. dry with materialwere dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified by flash chromatography on silica gel (1:0-9:1 dichloromethane/methanol)

Sources & evidence

ORD record
ord-4031287748bb48648e8300a06009e3b8
Source dataset
uspto-grants-2014_10
Patent number
US08853258B2

Reaction notes

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