Potassium Carbonate → N-{[5-Fluoro-7-(methylsulfonyl)-4H-1,3-benzodioxin-2-YL]methyl}propan-1-amine

HRID 452408노트

반응식

HRID 452408 반응식
Br[C:2]1[CH:3]=[C:4]([F:17])[C:5]2[CH2:10][O:9][CH:8]([CH2:11][NH:12][CH2:13][CH2:14][CH3:15])[O:7][C:6]=2[CH:16]=1.[CH3:18][S:19]([O-:21])=[O:20].[Na+].N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.[Cu](I)I.O.CCOC(C)=O>[F:17][C:4]1[C:5]2[CH2:10][O:9][CH:8]([CH2:11][NH:12][CH2:13][CH2:14][CH3:15])[O:7][C:6]=2[CH:16]=[C:2]([S:19]([CH3:18])(=[O:21])=[O:20])[CH:3]=1

참가 물질

9

반응물 4

HCID 11430Potassium CarbonateHCID 145742L-Proline2회HCID 2733271Sodium methanesulfinateHCID 44481627N-[(7-bromo-5-fluoro-4H-1,3-benzodioxin-2-yl)methyl]propan-1-amine

생성물 1

HCID 44481628N-{[5-Fluoro-7-(methylsulfonyl)-4H-1,3-benzodioxin-2-YL]methyl}propan-1-amine수율 39%

시약·촉매·용매 4

HCID 83717Copper iodide촉매2회HCID 679Dimethyl Sulfoxide용매HCID 962Water용매HCID 8857Ethyl Acetate용매

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온도
140 °C

실험 절차

A mixture of N-[(7-bromo-5-fluoro-4H-1,3-benzodioxin-2-yl)methyl]propan-1-amine (0.23 g, 0.76 mmol), sodium methanesulfinate (0.14 g, 1.13 mmol, 85%), copperiodide (14 mg, 0.08 mmol), L-proline (17 mg, 0.15 mmol), potassium carbonate (21 mg, 0.15 mmol) in DMSO (2.5 ml) was degassed with nitrogen. Heating in a microwave oven at 140° C. for 30 min afforded product, but the starting material was not completely converted. Additional copperiodide (14 mg, 0.08 mmol) and L-proline (17 mg, 0.15 mmol) were added and the mixture was heated once again at 140° C. for 30 min. The mixture was brought to ambient temperature and EtOAc (100 ml) and water (50 ml) were added. The phases were separated and the aqueous phase was extracted with EtOAc (3×50 ml). The organic phases were combined, dried (Na2SO4), filtered and evaporated. Purification had to be done three times, by flash column chromatography (EtOAc/MeOH 8:1) before affording the pure title compound (90 mg, 39%). The amine was converted into the hydrochloric acid salt and crystallized from EtOH/DEE (55 mg). M.p. 194° C. 1H-NMR (400 MHz, MeOH): δ 7.36 (2H, m), δ 5.26 (1H, t, J 4.8 Hz), δ 5.05 (2H, dd, J1 20.8 Hz, J2 16.0 Hz), δ 3.13 (3H, s), δ 2.99 (2H, m), δ 2.66 (2H, t, J 7.6 Hz), δ 1.56 (2H, m), δ 0.95 (3H, t, J 7.6 Hz).

후처리

  1. customwas degassed with nitrogen
  2. customafforded product
  3. temperaturethe mixture was heated once again at 140° C. for 30 min
  4. customwas brought to ambient temperature
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted with EtOAc (3×50 ml)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated
  10. customPurification

출처 및 근거

ORD 기록
ord-a8a4bb0d6e5e4ce194e8231f604d4620
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08492372B2

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