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

HRID 2188246

Reaction equation

HRID 2188246 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-fd09ac6d8db047268429823eed6650bc
Source dataset
uspto-grants-2002_06
Patent number
US06410728B1

Linked notes

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