Hydrochloric Acid → tert-Butyl 1H-pyrrol-1-ylcarbamate

HRID 1972707Notes

Reaction equation

HRID 1972707 reaction equation
[C:1]([O:5][C:6](=[O:9])[NH:7][NH2:8])([CH3:4])([CH3:3])[CH3:2].CO[CH:12]1[CH2:16][CH2:15][CH:14](OC)O1.Cl.C(=O)(O)[O-].[Na+]>O1CCOCC1.C(OCC)C.CO>[C:1]([O:5][C:6](=[O:9])[NH:7][N:8]1[CH:12]=[CH:16][CH:15]=[CH:14]1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 313Hydrochloric Acid2×HCID 70091tert-Butyl carbazateHCID 790982,5-DimethoxytetrahydrofuranHCID 516892Sodium Bicarbonate

Product 1

HCID 49760548tert-Butyl 1H-pyrrol-1-ylcarbamateYield 43.6%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A flask (fitted with a Dean-Stark trap) containing a stirred solution of tert-butylcarbazate (100, 0.757 mol), 2,5-dimethoxytetrahydrofuran (108 g, 0.832 mol) and 2N HCl (10 mL) in 1,4-dioxane (700 mL) was heated under nitrogen at 90° C. As the reaction progressed over several hours, the solution changed from pale yellow to orange and began to reflux. The reaction was monitored by the amount of distillate collected in the Dean-Stark trap (primarily CH3OH, 2 moles/1 mole reagent). As methanol collection approached the theoretical amount (50 mL), a sample was analyzed by TLC (silica gel, 1:3 EtOAc/hexane, ninhydrin stain) to confirm reaction completion. Heating was shut off and the reaction was allowed to cool somewhat before adding saturated, aq sodium bicarbonate solution (˜25 mL) to neutralize the hydrochloric acid. The quenched mixture was filtered through a sintered-glass funnel and concentrated in vacuo to leave an orange, semi-solid residue. The residue was suspended in diethyl ether (minimum volume) and the nearly colorless solids were collected by suction filtration, washed with hexane and air-dried to afford 60.2 g (40%) of product. A second crop (yellow-tan solids) from the mother liquors was isolated: 29.0 g (19%). 1H-NMR (CD3OD): δ10.23 (br s, 1H), 6.66 (t, 2H, J=2.2 Hz), 5.94 (t, 2H, J=2.2), 1.42 (s, 9H); MS: GC/MS (+esi): m/z=182.9 [MH]+

Workup

  1. customA flask (fitted with a Dean-Stark trap)
  2. waitAs the reaction progressed over several hours
  3. temperatureto reflux
  4. customAs methanol collection
  5. customreaction completion
  6. temperatureHeating
  7. temperatureto cool somewhat
  8. additionbefore adding saturated
  9. filtrationThe quenched mixture was filtered through a sintered-glass funnel
  10. concentrationconcentrated in vacuo
  11. customto leave an orange, semi-solid residue
  12. filtrationthe nearly colorless solids were collected by suction filtration
  13. washwashed with hexane
  14. customair-dried

Sources & evidence

ORD record
ord-d7f089119fad4ee781600a9f6becf816
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

Loading…