Acetonitrile → tert-Butyl (2-cyano-1H-pyrrol-1-yl)carbamate

HRID 73685

Reaktionsgleichung

Reaktionsgleichung von HRID 73685
[C:1]([O:5][C:6](=[O:13])[NH:7][N:8]1[CH:12]=[CH:11][CH:10]=[CH:9]1)([CH3:4])([CH3:3])[CH3:2].[C:14](#[N:16])C.ClS(N=C=O)(=O)=O.C1C=C2C(C(O)(O)C(=O)C2=CC=1)=O>CCOC(C)=O.C(OCC)(=O)C.CCCCCC.CN(C)C=O>[C:14]([C:9]1[N:8]([NH:7][C:6](=[O:13])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH:12]=[CH:11][CH:10]=1)#[N:16]

Komponenten

8

Edukt 4

HCID 6342AcetonitrileHCID 10236NinhydrinHCID 70918Chlorosulfonyl isocyanateHCID 49760548tert-Butyl 1H-pyrrol-1-ylcarbamate

Produkt 1

HCID 50999066tert-Butyl (2-cyano-1H-pyrrol-1-yl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 21226206Ethyl acetate hexaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A 2 L, 3-neck RB was fitted w/stir bar, N2 inlet, rubber septum low-temp. thermometer and ice/acetone cooling bath. Pyrrol-1-yl-carbamic acid tert-butyl ester (99.0 g, 0.543 mol) was added to the reactor, dissolved w/anhydrous acetonitrile (700 mL) and the stirred solution was cooled to 0° C. Chlorosulfonyl isocyanate (49.7 mL, 0.57 mol) was added dropwise via syringe (maintaining an internal temp. below 5° C.); after ˜20 minutes a suspension was observed. After 45 minutes N,N-dimethylformamide (anhydrous, 100 mL) was added dropwise via addition funnel (keeping internal temp. below 5° C.) and the reaction mixture became a solution. Stirring @ 0° C. was continued for 45 minutes, then the reaction was allowed to warm to RT; monitoring by TLC (silica gel, 1:3 ethyl acetate/hexane, UV, ninhydrin stain) of a quenched sample indicated that the reaction had progressed to completion. The mixture was poured onto ice (˜2 L) and stirred with addition of EtOAc (2 L). The layers were separated and the organic layer was dried over magnesium sulfate. The dried solution was filtered through a pad of 30/40 Magnesol and the filtrate was concentrated to dryness in vacuo, then the residue was dissolved in a minimum volume of dichloromethane and chromatographed on a plug of silica gel, eluting with ethyl acetate/hexane, 0-50% ethyl acetate. The clean, product-containing fractions were combined and concentrated to dryness in vacuo, to afford the desired product as a white solid, 69.8 g (62%). A somewhat impure fraction provided additional material, 16.8 g (15%), bringing the total recovery to 86.6 g, (77%). 1H-NMR (CD3OD): δ 7.01 (dd, 1H, J=3.0, 1.6 Hz), 6.82 (dd, 1H, J=4.4, 1.7 Hz), 6.19 (dd, 1H, J=4.2, 2.9 Hz), 4.88 (s, 1H, H2O+NH—), 1.50 (br s, 9H, HN—BOC); MS: LC/MS (+esi), m/z=207.9 [M+H].

Aufarbeitung

  1. customA 2 L, 3-neck RB was fitted
  2. temperaturemaintaining an internal temp
  3. custombelow 5° C.
  4. stirringStirring @ 0° C.
  5. waitwas continued for 45 minutes
  6. temperatureto warm to RT
  7. additionThe mixture was poured onto ice (˜2 L)
  8. customThe layers were separated
  9. dry with materialthe organic layer was dried over magnesium sulfate
  10. filtrationThe dried solution was filtered through a pad of 30/40 Magnesol
  11. concentrationthe filtrate was concentrated to dryness in vacuo
  12. dissolutionthe residue was dissolved in a minimum volume of dichloromethane
  13. customchromatographed on a plug of silica gel
  14. washeluting with ethyl acetate/hexane, 0-50% ethyl acetate
  15. additionThe clean, product-containing fractions
  16. concentrationconcentrated to dryness in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-f38c72d0b0714490b09d65a530b2f7db
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08829185B2

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