Ammonium Chloride → (S)-4-Benzyl-3-(2-(4-bromo-2-methylphenyl)acetyl)oxazolidin-2-one

HRID 708857Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 708857
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[C:4]([CH3:12])[CH:3]=1.C(Cl)(=O)C(Cl)=O.[CH2:19]([C@H:26]1[CH2:30][O:29][C:28](=[O:31])[NH:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C([Li])CCC.[Cl-].[NH4+]>C(Cl)Cl.C1COCC1.CN(C=O)C>[CH2:19]([C@H:26]1[CH2:30][O:29][C:28](=[O:31])[N:27]1[C:9](=[O:11])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=1[CH3:12])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Komponenten

9

Edukt 5

HCID 25517Ammonium ChlorideHCID 65578Oxalyl chlorideHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 190260522-(4-Bromo-2-methylphenyl)acetic acidHCID 178418339Butyllithium

Produkt 1

HCID 118093106(S)-4-Benzyl-3-(2-(4-bromo-2-methylphenyl)acetyl)oxazolidin-2-oneAusbeute 76 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To 16B (11 g, 48.0 mmol) in CH2Cl2 (200 ml) was added oxalyl chloride (7.36 ml, 84 mmol) and DMF (0.112 ml, 1.441 mmol). The reaction was stirred at rt for 2 h. The solvent was removed and chased with ethyl acetate (2×). The residue was dried under high vac for 1.5 h. To (S)-4-benzyloxazolidin-2-one (10.21 g, 57.6 mmol) in THF (200 ml) at −78° C. was added n-butyllithium (1.6 M in hexanes, 36.0 ml, 57.6 mmol). The reaction was stirred for 25 min at −78° C. Then the above acylchloride dissolved in THF (100 mL) was added. The reaction was stirred at −78° C. for 1 h and then at rt for 15 min. Sat ammonium chloride was added to quench the reaction and ethyl acetate to dilute the reaction. The organic layer was then washed with water, brine, dried over sodium sulfate and concentrated. The crude product was purified by flash chromatography (0-50% ethyl acetate/hexanes). The desired fractions were combined and concentrated to give 16C (14.1 g, 36.3 mmol, 76% yield) as a white solid. 1H NMR (400 MHz, chloroform-d) δ ppm 7.38 (d, J=1.77 Hz, 1H) 7.27-7.38 (m, 4H) 7.16-7.23 (m, 2H) 7.06 (d, J=8.08 Hz, 1H) 4.64-4.76 (m, 1H) 4.14-4.36 (m, 4H) 3.32 (dd, J=13.26, 3.16 Hz, 1H) 2.79 (dd, J=13.39, 9.60 Hz, 1H) 2.26-2.32 (m, 3H).

Aufarbeitung

  1. customThe solvent was removed
  2. customThe residue was dried under high vac for 1.5 h
  3. stirringThe reaction was stirred for 25 min at −78° C
  4. additionwas added
  5. stirringThe reaction was stirred at −78° C. for 1 h
  6. waitat rt for 15 min
  7. customto quench
  8. customthe reaction and ethyl acetate
  9. additionto dilute
  10. customthe reaction
  11. washThe organic layer was then washed with water, brine
  12. dry with materialdried over sodium sulfate
  13. concentrationconcentrated
  14. customThe crude product was purified by flash chromatography (0-50% ethyl acetate/hexanes)
  15. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-b20455f8a7554670b23d6ec0d9c93535
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09174974B2

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