N-methyl-2-pyrrolidone → 2-Chloro-6-isobutylisonicotinic acid tert-butyl ester

HRID 2040763Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2040763
[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:12]=[C:11]([Cl:13])[N:10]=[C:9](Cl)[CH:8]=1)([CH3:4])([CH3:3])[CH3:2].CN1C(=O)CCC1.[CH2:23]([Mg]Cl)[CH:24]([CH3:26])[CH3:25]>C1COCC1>[C:1]([O:5][C:6](=[O:15])[C:7]1[CH:8]=[C:9]([CH2:23][CH:24]([CH3:26])[CH3:25])[N:10]=[C:11]([Cl:13])[CH:12]=1)([CH3:2])([CH3:3])[CH3:4]

Komponenten

5

Edukt 3

HCID 13387N-methyl-2-pyrrolidoneHCID 22594123tert-Butyl 2,6-dichloropyridine-4-carboxylateHCID 178418368HCID 178418368, Verbindung

Produkt 1

HCID 866398762-Chloro-6-isobutylisonicotinic acid tert-butyl esterAusbeute 90 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of 2,6-dichloro-isonicotinic acid tert.-butyl ester (1.74 g, 7.0 mmol), Fe(acac)3 (706 mg, 2.0 mmol) and NMP (1.0 g, 10 mmol) in THF (250 mL), a solution of isobutylmagnesium chloride (1.15 g, 9.8 mmol) in THF is slowly added at −77° C. The brown solution turns turbid and black. Stirring is continued for 1 h at −72° C. before it is warmed to rt. The mixture is again cooled to −40° C. and then stirred for 16 h. The reaction is carefully quenched with 0.5 N aq. HCl (100 mL) and diluted with ether. The org. layer is separated and the aq. phase is extracted five more times with ether. The combined org. extracts are dried over MgSO4, filtered and evaporated. The crude product is purified by MPLC on silica gel to give 2-chloro-6-isobutylisonicotinic acid tert.-butyl ester as a pale yellow oil (1.70 g) which contains 2,6-di-isobutylisonicotinic acid tert.-butyl ester as an impurity; LC-MS: tR=1.12 min, [M+1]+=270.07.

Aufarbeitung

  1. temperatureThe mixture is again cooled to −40° C.
  2. stirringstirred for 16 h
  3. customThe reaction is carefully quenched with 0.5 N aq. HCl (100 mL)
  4. additiondiluted with ether
  5. customlayer is separated
  6. extractionthe aq. phase is extracted five more times with ether
  7. dry with materialextracts are dried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product is purified by MPLC on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-a40c5fd3833e4d899e9c3c3b1a534233
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08580824B2

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