Heptane → N-[2-cyclopropyl-1-methyl-1-(5-methylthiazol-2-yl)ethyl]-2-methyl-propane-2-sulfinamide

HRID 1480250

Reaktionsgleichung

Reaktionsgleichung von HRID 1480250
C([N-]C(C)C)(C)C.[Li+].[CH3:9][C:10]1[S:14][CH:13]=[N:12][CH:11]=1.[CH:15]1([CH2:18]/[C:19](=[N:21]/[S:22]([C:24]([CH3:27])([CH3:26])[CH3:25])=[O:23])/[CH3:20])[CH2:17][CH2:16]1.C[Al](C)C.CCCCCCC>C1COCC1.C1(C)C=CC=CC=1>[CH:15]1([CH2:18][C:19]([NH:21][S:22]([C:24]([CH3:25])([CH3:27])[CH3:26])=[O:23])([CH3:20])[C:13]2[S:14][C:10]([CH3:9])=[CH:11][N:12]=2)[CH2:16][CH2:17]1

Komponenten

8

Edukt 5

HCID 8900HeptaneHCID 1379805-MethylthiazoleHCID 2724682Lithium diisopropylamideHCID 16682925TrimethylaluminumHCID 89424933(NE)-N-(1-cyclopropylpropan-2-ylidene)-2-methylpropane-2-sulfinamide

Produkt 1

HCID 90204130N-[2-cyclopropyl-1-methyl-1-(5-methylthiazol-2-yl)ethyl]-2-methyl-propane-2-sulfinamideAusbeute 55 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittel2×HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

A 2.0M solution of lithium diisopropylamide in THF (745 μl, 1.49 mmol) was added dropwise to a solution of 5-methylthiazole (148 mg, 1.49 mmol) in dry THF (0.5 ml) cooled to −78° C. and once the addition was complete the reaction was stirred for 30 minutes at −78° C. followed by addition of dry toluene (1.5 ml). To a solution of (NE)-N-(2-cyclopropyl-1-methyl-ethylidene)-2-methyl-propane-2-sulfinamide (CAN 1426426-70-1, 150 mg, 745 μmol) in dry toluene (1.5 mL) was added a 2.0M solution of trimethylaluminum in heptane (410 μl, 820 μmol). The previous solution was then added to the reaction mixture cooled at −78° C. The reaction was allowed to warm up to room temperature overnight. The reaction was quenched by the addition of a saturated aqueous solution of ammonium chloride and was then diluted with ethyl acetate. The bi-phasic mixture was poured into a separatory funnel and extracted. The organic phase was collected, dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient to yield the title compound (123 mg, 55%). MS (ESI, m/z): 301.4 (M+H+).

Aufarbeitung

  1. additiononce the addition
  2. additionThe previous solution was then added to the reaction mixture
  3. temperaturecooled at −78° C
  4. temperatureto warm up to room temperature overnight
  5. customThe reaction was quenched by the addition of a saturated aqueous solution of ammonium chloride
  6. additionwas then diluted with ethyl acetate
  7. additionThe bi-phasic mixture was poured into a separatory funnel
  8. extractionextracted
  9. customThe organic phase was collected
  10. dry with materialdried over sodium sulfate
  11. customevaporated down to dryness
  12. customThe crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient

Quellen und Nachweise

ORD-Eintrag
ord-1e2c2ff3bbc14a9e8fe1d5f2c5b24baf
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09409866B2

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