Pyridine → 7-Bromo-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid methylamide

HRID 460288노트

반응식

HRID 460288 반응식
[Br:1][C:2]1[C:10]2[O:9][CH2:8][C:7]([CH3:12])([CH3:11])[C:6]=2[CH:5]=[C:4]([C:13]([OH:15])=O)[CH:3]=1.[CH3:16][N:17](C=O)C.Cl.CN.N1C=CC=CC=1>C1COCC1.C(OCC)(=O)C.O>[CH3:16][NH:17][C:13]([C:4]1[CH:3]=[C:2]([Br:1])[C:10]2[O:9][CH2:8][C:7]([CH3:12])([CH3:11])[C:6]=2[CH:5]=1)=[O:15]

참가 물질

8

반응물 4

HCID 1049PyridineHCID 6228DimethylformamideHCID 6364545Methylamine hydrochlorideHCID 220414067-Bromo-3,3-dimethyl-2,3-dihydrobenzofuran-5-carboxylic acid

생성물 1

HCID 695224787-Bromo-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid methylamide수율 223.8%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 7-bromo-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid (4.99 g, 18.41 mmol) in dry THF (40 mL) was added at room temperature thionychloride (2 mL, 27.61 mmol) and DMF (0.14 mL, 1.84 mmol). The reaction mixture was stirred 1 hr then methylamine hydrochloride (2.48 g, 36.82 mmol) was added followed by slow addition of pyridine (4.5 mL, 55.23 mmol). The reaction mixture was stirred overnight then water and ethyl acetate were added. The layers were separated. The aqueous layer was extracted twice with ethyl acetate. The combined extracts were washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was chromatographed on silica gel (50% to 100% ethyl acetate in hexane, then 40% MeOH in Ethyl acetate) to give 1.17 g of 7-bromo-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid methylamide (22%). 1H NMR (300 MHz; CDCl3): 1.36 (s, 6H), 2.99 (d, J=4.5 Hz, 3H), 4.39 (s, 2H), 6.25 (br s, 1H), 7.54 (d, J=1.5 Hz, 1H), 7.70 (d, J=1.5 Hz, 1H).

후처리

  1. stirringThe reaction mixture was stirred overnight
  2. customThe layers were separated
  3. extractionThe aqueous layer was extracted twice with ethyl acetate
  4. washThe combined extracts were washed successively with water and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was chromatographed on silica gel (50% to 100% ethyl acetate in hexane

출처 및 근거

ORD 기록
ord-996cdac4254441578be78053e653fca3
출처 데이터셋
uspto-grants-2007_03
특허 번호
US07196108B2

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