Hydrazine hydrate (1:1) → N-(((5S)-3-(4-ethynyl-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl)methyl)acetamide

HRID 2188244Notes

Reaction equation

HRID 2188244 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:13][CH:12]([CH2:14][N:15]3C(=O)C4[C:17](=CC=CC=4)[C:16]3=[O:25])[O:11][C:10]2=[O:26])=[CH:5][C:4]=1[F:27])#[CH:2].C1COCC1.C(O)C.O.NN>C1COCC1.ClCCl>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:13][C@H:12]([CH2:14][NH:15][C:16](=[O:25])[CH3:17])[O:11][C:10]2=[O:26])=[CH:5][C:4]=1[F:27])#[CH:2]

Participants

5

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 21873804Tetrahydrofuran ethanolHCID 224474732-(3-(4-Ethynyl-3-fluoro-phenyl)-2-oxo-oxazolidin-5-ylmethyl)-isoindole-1,3-dione

Product 1

HCID 59908254N-(((5S)-3-(4-ethynyl-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl)methyl)acetamide

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A 50° C. suspension of Example 3A (1.65 g) in 1:1 THF/ethanol (34 mL) was treated with hydrazine monohydrate (3×240 μL) at 1 hour intervals. One hour after the final addition the mixture was cooled to 25° C. and filtered. The filtrate was concentrated in vacuo. The resultant material was dissolved in a mixture of pyridine (17 mL) and dichloromethane (17 mL), cooled to −5° C., and treated with acetic anhydride (854 μL). The reaction mixture was warmed to room temperature, stirred for 5 minutes, and concentrated to provide crude product. The crude product was dissolved in 4:1 THF/dichloromethane (75 mL) and washed with 1:1 brine/water. The aqueous wash was extracted with dichloromethane (25 mL), and the combined extracts were dried over MgSO4. Next the mixture was filtered and concentrated. The residue was dissolved in acetone (20 mL) and filtered. The filtrate was concentrated and the residue triturated with hexanes to provide the desired product. MS (ESI(+)) m/e 277 (M+H)+; 1H NMR (300 MHz, CDCl3) δ 7.5-7.4 (m, 2H), 7.16-7.19 (dd, J=2.4, 8.4 Hz, 1H), 5.93 (bt, 1H), 4.8 (m, 1H), 4.05 (t, J=9 Hz, 1H), 3.8-3.6 (m, 3H), 3.28 (s, 1H), 2.02 (s, 3H).

Workup

  1. additionOne hour after the final addition the mixture
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated in vacuo
  4. dissolutionThe resultant material was dissolved in a mixture of pyridine (17 mL) and dichloromethane (17 mL)
  5. temperaturecooled to −5° C.
  6. additiontreated with acetic anhydride (854 μL)
  7. temperatureThe reaction mixture was warmed to room temperature
  8. concentrationconcentrated
  9. customto provide crude product
  10. washwashed with 1:1 brine/water
  11. washThe aqueous wash
  12. extractionwas extracted with dichloromethane (25 mL)
  13. dry with materialthe combined extracts were dried over MgSO4
  14. filtrationNext the mixture was filtered
  15. concentrationconcentrated
  16. dissolutionThe residue was dissolved in acetone (20 mL)
  17. filtrationfiltered
  18. concentrationThe filtrate was concentrated
  19. customthe residue triturated with hexanes

Sources & evidence

ORD record
ord-ef7f5a4cd9f04505895e11bf06db6663
Source dataset
uspto-grants-2002_06
Patent number
US06410728B1

Reaction notes

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