Triethylamine → 1-(t-Butoxycarbonyl)-3-(chloromethyl)-6-nitroindoline

HRID 1603039Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1603039
CS(Cl)(=O)=O.[C:6]([O:10][C:11]([N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[CH:15]([CH2:25]O)[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].CCN(CC)CC.S([O-])(=O)(=O)C.[Li+].[Cl-:40]>C(Cl)Cl.CN(C=O)C.O>[C:6]([O:10][C:11]([N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=2)[CH:15]([CH2:25][Cl:40])[CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7]

Komponenten

9

Edukt 5

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 433294Lithium ChlorideHCID 107561891-(t-Butyloxycarbonyl)-3-(hydroxymethyl)-6-nitroindoline

Produkt 1

HCID 108289531-(t-Butoxycarbonyl)-3-(chloromethyl)-6-nitroindolineAusbeute 87,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

Methanesulfonyl chloride (0.57 mL, 7.4 mmol) was added dropwise to a solution of 1-(t-butyloxycarbonyl)-3-(hydroxymethyl)-6-nitroindoline (1.21 g, 4.11 mmol) and Et3N (1.15 mL, 8.2 mmol) in CH2Cl2 (70 mL) at 0° C., and the pale yellow solution stirred for 5 min. Water was added, the mixture was extracted with CH2Cl2 (×2), and the extracts dried (Na2SO4) and evaporated. The crude mesylate was dissolved in DMF (10 mL) with LiCl (0.70 g, 16 mmol) and the mixture stirred at 80° C. under nitrogen for 1 h. The DMF was evaporated, the residue dissolved in EtOAc and water, extracted once more with EtOAc, and the organic extracts dried (Na2SO4) and evaporated. Dry column chromatography, eluting with EtOAc/petroleum ether (1:9), gave title compound as pale yellow foam (1.12 g, 87%). A sample was crystallised from benzene-petroleum ether to give a yellow crystalline solid, mp 111-111.5° C. 1H NMR (CDCl3) δ8.67, 8.34 (2 x br s, 1H, H-7), 7.86 (dd, J=8.2, 2.2 Hz, 1H, H-5), 7.35 (d, J=8.2 Hz, 1H, H-4), 4.22 (dd, J=11.6, 9.6 Hz, 1H, H-2), 4.04-3.97 (m, 1H, H-2), 3.82-3.74 (m, 2H, CHHCl, H-3), 3.68-3.62 (m, 1H, CHHCl), 1.60 (s, 9H, t-Bu); 13C NMR δ151.8, 149.0, 144 (br), 138 (br) (C-6,8,9, NCO2), 124.6, 117.8, 110.0 (C-4,5,7), 82.0 (OCMe3), 52.4 (C-2), 46.3 (CH2Cl), 41.7 (C-3), 28.4 (C(CH3)3). Anal. Calculated for C14H18ClN2O4 : C, 53.8; H, 5.5; N, 11.3; Cl, 11.3. Found: C, 54.0; H, 5.5; N, 9.1; Cl, 11.5%.

Aufarbeitung

  1. extractionthe mixture was extracted with CH2Cl2 (×2)
  2. dry with materialthe extracts dried (Na2SO4)
  3. customevaporated
  4. stirringthe mixture stirred at 80° C. under nitrogen for 1 h
  5. customThe DMF was evaporated
  6. dissolutionthe residue dissolved in EtOAc
  7. extractionwater, extracted once more with EtOAc
  8. dry with materialthe organic extracts dried (Na2SO4)
  9. customevaporated
  10. customDry column chromatography
  11. washeluting with EtOAc/petroleum ether (1:9)

Quellen und Nachweise

ORD-Eintrag
ord-1785b780f05549419c983e8b59a26eb5
Quelldatensatz
uspto-grants-1999_11
Patentnummer
US05985909

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