L-Proline → 3'-{[3-(methylsulfonyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,1'-inden]-2'(3'H)-one

HRID 1407836

반응식

HRID 1407836 반응식
Br[C:2]1[C:3]([CH2:8][CH:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]3([C:29]4[C:20](=[CH:21][C:22]5[O:27][CH2:26][CH2:25][O:24][C:23]=5[CH:28]=4)[O:19][CH2:18]3)[C:10]2=[O:30])=[N:4][CH:5]=[CH:6][CH:7]=1.[CH3:31][S:32]([O-])(=[O:34])=[O:33].[Na+].[Na].N1CCC[C@H]1C(O)=O>CS(C)=O.C(OCC)(=O)C.[Cu](I)I>[CH3:31][S:32]([C:2]1[C:3]([CH2:8][CH:9]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[C:11]3([C:29]4[C:20](=[CH:21][C:22]5[O:27][CH2:26][CH2:25][O:24][C:23]=5[CH:28]=4)[O:19][CH2:18]3)[C:10]2=[O:30])=[N:4][CH:5]=[CH:6][CH:7]=1)(=[O:34])=[O:33]

참가 물질

8

반응물 4

HCID 145742L-ProlineHCID 638112Sodium methanesulfonateHCID 5360545SodiumHCID 673576033'-[(3-Bromopyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]-benzodioxine-8,1'-inden]-2'(3'H)-one

생성물 1

HCID 673565253'-{[3-(methylsulfonyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,1'-inden]-2'(3'H)-one수율 44.4%

시약·촉매·용매 3

HCID 83717Copper iodide촉매HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매

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온도
95 °C

실험 절차

A mixture of 3′-[(3-bromopyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,1′-inden]-2′(3′H)-one (0.233 g, 0.50 mmol), sodium methanesulfonate (0.071 g, 0.60 mmol), copper iodide (0.010 g, 0.05 mmol), and the sodium salt of L-proline (0.014 g, 0.10 mmol) were combined in dimethyl sulfoxide (1 mL) and heated at 95° C. for 48 h, then stirred at ambient temperature for 30 h. The reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (100 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was triturated from methanol and further purified by column chromatography, and eluted with a 0% to 50% gradient of ethyl acetate in dichloromethane to yield 3′-{[3-(methylsulfonyl)pyridin-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,1′-inden]-2′(3′H)-one (0.103 g, 44%) as a colorless solid: mp>250° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.69 (d, J=4.2 Hz, 1H), 8.35 (dd, J=8.0, 0.5 Hz, 1H), 7.64 (dd, J=7.9, 4.7 Hz, 1H), 7.24 (dd, J=7.7, 7.7 Hz, 1H), 7.18 (d, J=7.3 Hz, 1H), 7.05-6.99 (m, 2H), 6.50 (s, 1H), 6.39 (s, 1H), 5.50 (ABq, 2H), 4.76 (ABq, 2H), 4.19-4.12 (m, 4H), 3.52 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 177.6, 155.0, 153.7, 153.6, 144.6, 143.4, 138.4, 138.2, 135.9, 132.4, 129.1, 124.1, 123.9, 123.3, 122.1, 112.2, 109.8, 99.1, 79.6, 64.7, 64.1, 57.7, 44.2, 42.7; MS (ES+) m/z 465.0 (M+1).

후처리

  1. washwashed with water (100 mL)
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was triturated from methanol
  6. customfurther purified by column chromatography
  7. washeluted with a 0% to 50% gradient of ethyl acetate in dichloromethane

출처 및 근거

ORD 기록
ord-a02796799cd54b38bddde3c1080cadb1
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08916580B2

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