Potassium Carbonate → tert-Butyl (2-amino-4-(thiophen-2-yl)phenyl)carbamate

HRID 1984770Notes

Reaction equation

HRID 1984770 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[C:4]([N+:16]([O-])=O)[CH:3]=1.[S:19]1[CH:23]=[CH:22][CH:21]=[C:20]1B(O)O.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C(OCC)(=O)C>[NH2:16][C:4]1[CH:3]=[C:2]([C:20]2[S:19][CH:23]=[CH:22][CH:21]=2)[CH:7]=[CH:6][C:5]=1[NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27339602-Thiopheneboronic acidHCID 52904808tert-Butyl (4-bromo-2-nitrophenyl)carbamate

Product 1

HCID 57717474tert-Butyl (2-amino-4-(thiophen-2-yl)phenyl)carbamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of tert-butyl (4-bromo-2-nitrophenyl)carbamate (19.4 g, 61.2 mmol), thiophene-2-boronic acid (9.94 g, 77.7 mmol) and K2CO3 (22.2 g, 160 mmol) in 60 mL of dioxane and 60 mL of water was degassed by bubbling nitrogen through the mixture for 30 min. Next, Pd[PPh3]4 (5.25 g, 4.53 mmol) was added and the heterogeneous mixture was warmed to reflux for 20 h. The mixture was cooled and diluted with ethyl acetate, washed with water and brine, dried (MgSO4), and concentrated. The resulting solid was dissolved in diethylether (500 mL) and filtered through a pad of silica. The solvents were removed under reduced pressure to yield the yellow-brown solid: 1H NMR (600 MHz, CDCl3): δ 9.65 (s, 9H), 8.58 (d, J=8.8 Hz, 1H), 8.39 (d, J=2.1 Hz, 1H), 7.81 (dd, J=8.8, 1.8 Hz, 1 H), 7.32 (m, 2H), 7.09 (dd, J=5.3, 3.8 Hz, 1H), 1.54 (s, 9H); MS (ESI+): cal'd [M+Na]+ 343.1, obs'd 343.1.

Workup

  1. customwas degassed
  2. customby bubbling nitrogen through the mixture for 30 min
  3. temperaturethe heterogeneous mixture was warmed
  4. temperatureto reflux for 20 h
  5. temperatureThe mixture was cooled
  6. washwashed with water and brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. dissolutionThe resulting solid was dissolved in diethylether (500 mL)
  10. filtrationfiltered through a pad of silica
  11. customThe solvents were removed under reduced pressure
  12. customto yield the yellow-brown solid

Sources & evidence

ORD record
ord-410b4851a5d5403e9c0c6656b6aca395
Source dataset
uspto-grants-2009_06
Patent number
US07544695B2

Reaction notes

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