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

HRID 1972708Notes

Reaction equation

HRID 1972708 reaction equation
[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]

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
0 °C

Procedure

A 2 L, 3-neck flask was fitted with stir bar, N2 inlet, rubber septum, 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 with 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 temperature 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 temperature below 5° C.) and the reaction mixture became a solution. Stirring at 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 Hi), 6.19 (dd, 1H, J=4.2, 2.9 Hz), 4.88 (s, 1H), 1.50 (br s, 9H); MS: LC/MS (+esi), m/z=207.9 [M+H].

Workup

  1. customA 2 L, 3-neck flask was fitted
  2. temperaturemaintaining an internal temperature below 5° C.)
  3. waitAfter 45 minutes
  4. stirringStirring at 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

Sources & evidence

ORD record
ord-2b681bbb34e747d2a9bdac4749156b4a
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

Loading…