Acetic Acid → tert-butyl {(5S)-3-[3-fluoro-4(4-morpholinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methylcarbamate

HRID 890636Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 890636
[C:1]1([CH2:7][O:8][C:9](=[O:24])[NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[C:13]([F:23])[CH:12]=2)C=CC=CC=1.O1C[C@@H]1C[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33].[CH3:37]C(C)([O-])C.[Li+].C(O)(=O)C>C1COCC1.O.C(Cl)Cl>[F:23][C:13]1[CH:12]=[C:11]([N:10]2[CH2:37][C@H:7]([CH2:1][NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[O:8][C:9]2=[O:24])[CH:16]=[CH:15][C:14]=1[N:17]1[CH2:18][CH2:19][O:20][CH2:21][CH2:22]1

Komponenten

8

Edukt 4

HCID 176Acetic AcidHCID 5306150Carbamic acid, N-(3-fluoro-4-(4-morpholinyl)phenyl)-, phenylmethyl esterHCID 10080852(S)-N-Boc-2,3-epoxypropylamineHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)

Produkt 1

HCID 11418025tert-butyl {(5S)-3-[3-fluoro-4(4-morpholinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methylcarbamate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a slurry of [3-fluoro-4(4-morpholinyl)phenyl]carbamic acid phenylmethyl ester (Example 1) (1.0039 g, 3.039 mmol) and tert-butyl (2S)oxiranylmethylcarbamate (Example 5) (0.653 g, 3.77 mmol, 1.24 eq) in THF (1.5 ml) at 0° C. was added a solution of lithium t-butoxide in THF (18.07 wt %, 1.735 g, 3.92 mmol, 1.29 eq). After standing 2 days at 20–25° C., methylene chloride (5.0 ml), then acetic acid (0.35 ml, 6.11 mmol, 2.01 eq) followed by water (3.5 ml) was added. The phases were separated and the aqueous washed with methylene chloride (3.5 ml). The combined organics were dried on magnesium sulfate and concentrated to an oil which was shown to contain 1.03 g (85.7%) of Compound III, wherein R1=3-fluoro-4-(4-morpholinyl)phenyl, R3=t-butyl, by external standard HPLC: retention time=4.06 min (column=Zorbax SB-C8 3.5 micron 150×4.6 mm, flow rate=2.0 ml/min, gradient elution from 30:70 A:B to 90:10 A:B over 15 minutes; A=969:30:1 acetonitrile: THF: trifluoroacetic acid; B=949:50:1 water: THF:trifluroracetic acid).

Aufarbeitung

  1. additionwas added
  2. customThe phases were separated
  3. washthe aqueous washed with methylene chloride (3.5 ml)
  4. customThe combined organics were dried on magnesium sulfate
  5. concentrationconcentrated to an oil which
  6. wash3.5 micron 150×4.6 mm, flow rate=2.0 ml/min, gradient elution from 30:70 A:B to 90:10 A:B over 15 minutes

Quellen und Nachweise

ORD-Eintrag
ord-85c960d6e7694e318507a98af7a38236
Quelldatensatz
uspto-grants-2006_02
Patentnummer
US06998420B2

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