Iodine → HCID 86701271, 화합물

HRID 2276072노트

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HRID 2276072 반응식
II.[C:3]([O:8][C@@H:9]1[C@@H:17]([CH2:18][CH2:19]I)[C:16](=[O:21])[O:15][CH2:14][C@H:13]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:12](=[O:30])[O:11][C@H:10]1[CH3:31])(=[O:7])[CH:4]([CH3:6])[CH3:5].F[C:33]1[CH:38]=[CH:37][C:36](I)=[CH:35][CH:34]=1>CN(C=O)C.CCOC(C)=O.[Zn].CC1C=CC=CC=1[P](C1C=CC=CC=1C)([Pd](Cl)(Cl)[P](C1=C(C)C=CC=C1)(C1C=CC=CC=1C)C1C=CC=CC=1C)C1C=CC=CC=1C>[C:3]([O:8][C@@H:9]1[C@@H:17]([CH2:18][CH2:19][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:16](=[O:21])[O:15][CH2:14][C@H:13]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:12](=[O:30])[O:11][C@H:10]1[CH3:31])(=[O:7])[CH:4]([CH3:6])[CH3:5]

참가 물질

8

반응물 3

HCID 807IodineHCID 96054-FluoroiodobenzeneHCID 86701268HCID 86701268, 화합물

생성물 1

HCID 86701271HCID 86701271, 화합물수율 51%

시약·촉매·용매 4

HCID 23994Zinc촉매HCID 178424406HCID 178424406, 화합물촉매HCID 6228Dimethylformamide용매3회HCID 8857Ethyl Acetate용매

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온도
40 °C

실험 절차

To an oven-dried flask containing a magnetic stir bar was added freshly ground zinc dust (149 mg, 2.28 mmol) and a small volume of DMF (100 μL) was added to just cover the dust. Iodine (57 mg, 0.23 mmol) was added and the mixture stirred for 2 min and then warmed to 40° C. A solution of (3S,6S,7R,8R)-3-(tert-butoxycarbonylamino)-8-(2-iodoethyl)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate (200 mg, 0.38 mmol) in DMF (1 mL) was added slowly at 40° C. After 15 min, the reaction mixture was cooled to ambient temperature (about 22° C.), and a solution of Pd((o-tol)3P)2Cl2 (7.5 mg, 0.01 mmol) and 1-fluoro-4-iodobenzene (58 uL, 0.49 mmol) in DMF (900 μL) was added to the reaction and the reaction was warmed back to 40° C. and stirring continued for 2.5 h. The mixture was cooled, diluted with EtOAc (2 mL) and filtered through a 0.45 μm fritted filter disc. The filtrate was diluted with EtOAc (20 mL), washed with saturated NaHCO3 solution (15 mL), dried over Na2SO4, filtered, and concentrated. Purification by column chromatography (SiO2, hexanes/EtOAc gradient) gave the title compound (92 mg, 51%) as a white glassy solid: 1H NMR (300 MHz, CDCl3) δ 7.31-7.14 (m, 3H), 7.14-7.04 (m, 2H), 5.46-5.15 (m, 2H), 5.06 (t, J=9.9 Hz, 1H), 4.91-4.72 (m, 2H), 3.61 (s, 1H), 2.76-2.48 (m, 3H), 2.40 (dt, J=13.8, 8.2 Hz, 1H), 2.17-1.99 (m, 1H), 1.73-1.52 (m, 1H), 1.45 (s, 9H), 1.25 (d, J=6.3 Hz, 3H), 1.16 (d, J=7.0 Hz, 6H); ESIMS m/z 500 ([M+Na]+).

후처리

  1. additionTo an oven-dried flask containing a magnetic stir bar
  2. waitAfter 15 min
  3. temperaturethe reaction mixture was cooled to ambient temperature (about 22° C.)
  4. temperaturethe reaction was warmed back to 40° C.
  5. stirringstirring
  6. waitcontinued for 2.5 h
  7. temperatureThe mixture was cooled
  8. filtrationfiltered through a 0.45 μm fritted filter disc
  9. additionThe filtrate was diluted with EtOAc (20 mL)
  10. washwashed with saturated NaHCO3 solution (15 mL)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customPurification by column chromatography (SiO2, hexanes/EtOAc gradient)

출처 및 근거

ORD 기록
ord-9ba797fd84b74535b1f91f14c3c7217a
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09131690B2

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