Ethyl Acetate → (R)-tert-butyl 8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2(1H)-carboxylate

HRID 1482981Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1482981
[CH:1]([C@H:4]1[N:9]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:8][CH2:7][N:6]2[C:17]3[CH:23]=[C:22]([S:24]([CH3:27])(=[O:26])=[O:25])[C:21]([C:28](OC)=[O:29])=[CH:20][C:18]=3[N:19]=[C:5]12)([CH3:3])[CH3:2].CC(C[AlH]CC(C)C)C.CCOC(C)=O>C(Cl)Cl>[OH:29][CH2:28][C:21]1[C:22]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:23][C:17]2[N:6]3[CH2:7][CH2:8][N:9]([C:10]([O:12][C:13]([CH3:15])([CH3:16])[CH3:14])=[O:11])[C@H:4]([CH:1]([CH3:2])[CH3:3])[C:5]3=[N:19][C:18]=2[CH:20]=1

Komponenten

5

Edukt 3

HCID 8857Ethyl AcetateHCID 14487Diisobutylaluminum hydrideHCID 89815749(R)-2-tert-butyl 8-methyl 1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2,8 (1H)-dicarboxylate

Produkt 1

HCID 89815566(R)-tert-butyl 8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2(1H)-carboxylateAusbeute 74,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a 50 mL three-necked flask containing (R)-2-tert-butyl 8-methyl 1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2,8(1H)-dicarboxylate (250 mg, 0.554 mmol, from preparation 2) in DCM (5 mL) was added DIBAL-H (1.70 mL, 1.67 mmol, 1.0 M in toluene) dropwise at −78° C. under N2. The mixture was stirred at −78° C. for 3 h. The reaction was quenched with sat. aq. ammonium chloride (10 mL) at −78° C. The aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with water (15 mL) and brine, and then dried over anhydrous Na2SO4. The mixture was filtered and the filtrate was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with PE:EtOAc 8:1˜2:1 to give (R)-tert-butyl 8-(hydroxymethyl)-1-isopropyl-7-(methylsulfonyl)-3,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrazine-2(1H)-carboxylate (175 mg, 74.1% yield) as a white solid.

Aufarbeitung

  1. customThe reaction was quenched with sat. aq. ammonium chloride (10 mL) at −78° C
  2. extractionThe aqueous layer was extracted with EtOAc (3×20 mL)
  3. washThe combined organic layers were washed with water (15 mL) and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationThe mixture was filtered
  6. customthe filtrate was evaporated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel eluting with PE

Quellen und Nachweise

ORD-Eintrag
ord-a21f20b86625463e8f0e0034f5b231ae
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09416135B2

Notizen zur Reaktion

Wird geladen…