N-Fluorobenzenesulfonimide → Methyl 2-fluoro-2-(quinolin-6-yl)propanoate

HRID 219208

Reaktionsgleichung

Reaktionsgleichung von HRID 219208
[N:1]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]([CH3:16])[C:12]([O:14][CH3:15])=[O:13])=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:37])(=O)=O)=CC=1>C1COCC1>[F:37][C:11]([C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][CH:8]=1)[N:1]=[CH:2][CH:3]=[CH:4]2)([CH3:16])[C:12]([O:14][CH3:15])=[O:13]

Komponenten

5

Edukt 3

HCID 588007N-FluorobenzenesulfonimideHCID 2733832Lithium HexamethyldisilazideHCID 57691200Methyl 2-(quinolin-6-YL)propanoate

Produkt 1

HCID 67503402Methyl 2-fluoro-2-(quinolin-6-yl)propanoateAusbeute 75,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of methyl 2-(quinolin-6-yl)propanoate (0.868 g, 4.03 mmol) in THF (1.1M, 3.7 mL) at −78° C. was added LiHMDS (1M in THF) (5.24 ml, 5.24 mmol). The reaction was stirred at −78° C. for ˜15 minutes, then to it was added a solution of N-fluorobenzenesulfonimide (1.40 g, 4.44 mmol) in THF(1.0M, 4.5 mL). The reaction was allowed to warm to −10° C. over 2 h. The reaction was filtered through a plug of Celite, washed with EtOAc and the filtrate was then concentrated in vacuo. The concentrated material was rediluted with EtOAc and washed with saturated NH4Cl solution. The aqueous layer was then extracted with EtOAc, and the organic layers were dried over MgSO4, filtered and concentrated in vacuo. The crude material was dissolved in minimal DCM and purified via MPLC (eluting with isocratic 40% EtOAc:Hexanes to yield methyl 2-fluoro-2-(quinolin-6-yl)propanoate (0.709 g, 75.4% yield) as a yellow oil. To synthesize the corresponding acid, methyl 2-fluoro-2-(quinolin-6-yl)propanoate was saponified in a method similar to that of 2-(quinolin-6-yl)propanoic acid.

Aufarbeitung

  1. temperatureto warm to −10° C. over 2 h
  2. filtrationThe reaction was filtered through a plug of Celite
  3. washwashed with EtOAc
  4. concentrationthe filtrate was then concentrated in vacuo
  5. additionThe concentrated material was rediluted with EtOAc
  6. washwashed with saturated NH4Cl solution
  7. extractionThe aqueous layer was then extracted with EtOAc
  8. dry with materialthe organic layers were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe crude material was dissolved in minimal DCM
  12. custompurified via MPLC (
  13. washeluting with isocratic 40% EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-505a7b3ce08c41efa63213b15a3d9789
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08198448B2

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