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

HRID 452408ノート

反応式

HRID 452408 の反応式
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

参加物

9

反応物 4

HCID 11430Potassium CarbonateHCID 145742L-Proline2 回HCID 2733271Sodium methanesulfinateHCID 44481627N-[(7-bromo-5-fluoro-4H-1,3-benzodioxin-2-yl)methyl]propan-1-amine

生成物 1

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

試薬・触媒・溶媒 4

HCID 83717Copper iodide触媒2 回HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
140 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-a8a4bb0d6e5e4ce194e8231f604d4620
出典データセット
uspto-grants-2013_07
特許番号
US08492372B2

反応ノート

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