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

HRID 533529ノート

反応式

HRID 533529 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 313Hydrochloric Acid溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-4031287748bb48648e8300a06009e3b8
出典データセット
uspto-grants-2014_10
特許番号
US08853258B2

反応ノート

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