Water → Sutezolid

HRID 2294079Notes

Reaction equation

HRID 2294079 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:14]2[CH2:18][CH:17]([CH2:19][N:20]=[N+]=[N-])[O:16][C:15]2=[O:23])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][S:11][CH2:10][CH2:9]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.N1C=CC=CC=1.[CH3:50][C:51](OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=[O:52]>C1COCC1.C(Cl)Cl.CO.C(Cl)(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([N:14]2[CH2:18][C@H:17]([CH2:19][NH:20][C:51](=[O:52])[CH3:50])[O:16][C:15]2=[O:23])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][S:11][CH2:10][CH2:9]1

Participants

9

Reactant 5

HCID 962Water2×HCID 1049PyridineHCID 11776TriphenylphosphineHCID 613145Acetic acid 10-acetoxymethyl-anthracen-9-ylmethyl esterHCID 53649865HCID 53649865, compound

Product 1

HCID 465951SutezolidYield 72%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 21584188Chloroform methanolSolvent3×

Conditions

Temperature
50 °C

Procedure

The crude [[3-[3-fluoro-4-(4-thiomorpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]azide (889 mg, 2.635 mmol) was dissolved in dry THF (15 mL) and treated with triphenylphosphine (864 mg, 3.294 mmol). After an hour, the reaction was found to be complete by TLC (10% MeOH/CHCl3, UV short wave). Next, water (0.949 mL, 52.7 mmol) was added and the reaction was heated to 50° C. for two hours. At this point, the reaction was incomplete; so more water (0.475 mL, 26.35 mmol) was added and the reaction was heated to 60° C. for 5 hours. The reaction was then allowed to cool to ambient temperature, stirring overnight (11 hours) under N2. In the morning, the reaction was found to be complete by TLC (10% MeOH/CHCl3, UV short wave). The reaction was concentrated and then dried under high vacuum for two hours. Next, the semi-solid was dissolved in CH2Cl2 (15 mL) and treated with pyridine (0.320 mL, 3,953 mmol). The reaction was allowed to stir for 15 minutes and then the acetic arthydride (0.497 mL, 5.270 mmol) was added dropwise. After an hour, the reaction was complete by TLC (10% MeOH/CHCl3, UV short wave). The reaction mixture was diluted with CH2Cl2 (50 mL) and then washed with 1 N HCl (50 mL), saturated NaHCO3 (50 mL), and brine (50 mL). Each aqueous portion was back-extracted with more CH2Cl2 (2×20 mL each). The organic portions were combined, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield a white solid. This crude material was chromatographed on silica gel (100 g, packed with 10% CH3CN/CHCl3), eluting with 1-2% MeOH in 10% CH3CN/CHCl3 to give 667 mg (72%) of the title compound as a white solid with a melting point of 185.5°-186.5° C. and a HRMS (M+) calculated for C16H20N3O3FS 353.1209, found 353.1200.

Workup

  1. waitAfter an hour
  2. temperaturethe reaction was heated to 60° C. for 5 hours
  3. temperatureto cool to ambient temperature
  4. concentrationThe reaction was concentrated
  5. customdried under high vacuum for two hours
  6. dissolutionNext, the semi-solid was dissolved in CH2Cl2 (15 mL)
  7. stirringto stir for 15 minutes
  8. waitAfter an hour
  9. washwashed with 1 N HCl (50 mL), saturated NaHCO3 (50 mL), and brine (50 mL)
  10. extractionEach aqueous portion was back-extracted with more CH2Cl2 (2×20 mL each)
  11. dry with materialdried over anhydrous Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customto yield a white solid
  15. customThis crude material was chromatographed on silica gel (100 g, packed with 10% CH3CN/CHCl3)
  16. washeluting with 1-2% MeOH in 10% CH3CN/CHCl3

Sources & evidence

ORD record
ord-136f88631be343d5bef9bc0824966223
Source dataset
uspto-grants-1997_11
Patent number
US05688792

Reaction notes

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