Dimethyl (diazomethyl)phosphonate → 2-(3-(3-Fluoro-4-prop-1-ynyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl)-isoindole-1,3-dione

HRID 2188246

반응식

HRID 2188246 반응식
[CH3:1]C(C)([O-])C.[K+].[N+](=CP(=O)(OC)OC)=[N-].[C:16]([C:18]1[CH:23]=[CH:22][C:21]([N:24]2[CH2:28][CH:27]([CH2:29][N:30]3[C:38](=[O:39])[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[C:31]3=[O:40])[O:26][C:25]2=[O:41])=[CH:20][C:19]=1[F:42])#[CH:17]>C1COCC1>[F:42][C:19]1[CH:20]=[C:21]([N:24]2[CH2:28][CH:27]([CH2:29][N:30]3[C:31](=[O:40])[C:32]4[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=4)[C:38]3=[O:39])[O:26][C:25]2=[O:41])[CH:22]=[CH:23][C:18]=1[C:16]#[C:17][CH3:1]

참가 물질

5

반응물 3

HCID 5115033Dimethyl (diazomethyl)phosphonateHCID 224474732-(3-(4-Ethynyl-3-fluoro-phenyl)-2-oxo-oxazolidin-5-ylmethyl)-isoindole-1,3-dioneHCID 23665647Potassium tert-butoxide

생성물 1

HCID 224474862-(3-(3-Fluoro-4-prop-1-ynyl-phenyl)-2-oxo-oxazolidin-5-ylmethyl)-isoindole-1,3-dione

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
-78 °C

실험 절차

To a −78° C. solution of potassium t-butoxide (17 mL of a 1.0 M solution in THF) was added a −78° C. THF (4 mL) solution of dimethyl diazomethylphosphonate (2.53 g, prepared according to the procedure described in J. Org. Chem. 1971, 36, 1379-1385). The mixture was stirred at −78° C. for 10 minutes then a −78° C. solution of Example 3A (5.19 g) in THF (100 mL) was added via cannula over 20 minutes. The reaction mixture was stirred for 24 hours, gradually warming to room temperature. The mixture was quenched with 1:1 saturated ammonium chloride/water (200 mL) and extracted with dichloromethane (50 mL). The aqueous layer was extracted with 4:1 THF/dichloromethane (250 mL), and the combined extracts were washed with 1:1 saturated sodium bicarbonate/water (200 mL) and 1:1 brine/water (200 mL). The organic extracts were dried over MgSO4, filtered, and concentrated to provide crude product. The crude product was purified by flash column chromatography on silica gel eluting with 4:1 hexanes/acetone to provide the desired product. MS (ESI(+)) m/e 379 (M+H)+; 1H NMR (300 MHz, CDCl3) δ 7.9 (m, 2H), 7.77 (m, 2H), 7.45 (dd, J=2.4, 9 Hz, 1H), 7.36 (d, J=7.2 Hz, 1H), 7.25-7.35 (dd, J=2.4, 8.7 Hz, 1H), 4.97 (m, 1H), 4.07-4.18 (m, 2H), 3.8-4.01 (m, 2H), 2.09 (s, 3H).

후처리

  1. stirringThe reaction mixture was stirred for 24 hours
  2. temperaturegradually warming to room temperature
  3. customThe mixture was quenched with 1:1 saturated ammonium chloride/water (200 mL)
  4. extractionextracted with dichloromethane (50 mL)
  5. extractionThe aqueous layer was extracted with 4:1 THF/dichloromethane (250 mL)
  6. washthe combined extracts were washed with 1:1 saturated sodium bicarbonate/water (200 mL) and 1:1 brine/water (200 mL)
  7. dry with materialThe organic extracts were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto provide crude product
  11. customThe crude product was purified by flash column chromatography on silica gel eluting with 4:1 hexanes/acetone

출처 및 근거

ORD 기록
ord-fd09ac6d8db047268429823eed6650bc
출처 데이터셋
uspto-grants-2002_06
특허 번호
US06410728B1

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