2,6-Lutidine → 2-Amino-4-bromobenzonitrile

HRID 1520107Notes

Reaction equation

HRID 1520107 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](=[N:12]O)C(=O)[NH:8]2)=[CH:4][CH:3]=1.N1C(C)=CC=CC=1C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C1CCN2C(=NCCC2)CC1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:8][C:9]1[CH:10]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=1[C:6]#[N:12]

Participants

7

Reactant 5

HCID 79372,6-LutidineHCID 67749Trifluoromethanesulfonic anhydrideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516892Sodium BicarbonateHCID 178516984HCID 178516984, compound

Product 1

HCID 99206362-Amino-4-bromobenzonitrileYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cold solution of oxime (10) (8 g, 33.33 mmol) in CH2Cl2 (200 mL) at 0° C. was added 2,6-lutidine (4.5 mL, 38.7 mmol), followed by the dropwise addition of triflouromethanesulfonic anhydride (5.6 mL, 33.33 mmol). The cooling bath was removed, and the mixture was heated to reflux for 3 h. The reaction mixture was cooled to room temperature, and DBU (9.9 mL, 66.66 mmol) was added dropwise while maintaining the internal temperature of the reaction below 30° C. The mixture was further stirred at room temperature for 1 h and poured with vigorous stirring into excess dilute NaHCO3. This mixture was then stirred for several minutes, and the organic layer was separated. The aqueous layer was re-extracted with CH2Cl2 (100 mL×2). The combined extracts were dried with MgSO4 and concentrated to leave a dark brown solid, which was passed through a short silica column, eluting with CH2Cl2 (100%). The resulting fraction was dried under vacuum, triturated with CH2Cl2/hexanes, and the solid formed was filtered and dried under vacuum to afford 5.36 g (82%) of 11 as a light yellow solid. IR (KBr) νmax. cm−1: 3436, 3310 (NH2), 3032 (Ar—H), 2920 (Alph-H), 2246 (CN), 1610, 1512, 1418 (C═C). 1H NMR (500 MHz, CDCl3) δ=4.47 (br. s, 2H, NH2); 6.88 (dd, 1H, J=2.8, 8.2 Hz, H-5); 6.94 (br. s, 1H, H-3); 7.24 (d, 1H, J=8.2 Hz, H-6); 13C NMR (125.7 MHz, CDCl3) δ=95.17 (C-1), 117.16 (CN), 118.15 (C-3), 121.60 (C-5), 129.03 (C-4), 133.60 (C-6), 150.47 (C-2). Calculated (%) for C7H5BrN2 (195.96); C: 42.67, H: 2.56, N: 14.22. found (%); C: 42.60, H: 2.61, N: 14.17.

Workup

  1. customThe cooling bath was removed
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 3 h
  4. temperaturewhile maintaining
  5. customthe internal temperature of the reaction below 30° C
  6. additionpoured
  7. stirringThis mixture was then stirred for several minutes
  8. customthe organic layer was separated
  9. extractionThe aqueous layer was re-extracted with CH2Cl2 (100 mL×2)
  10. dry with materialThe combined extracts were dried with MgSO4
  11. concentrationconcentrated
  12. customto leave a dark brown solid, which
  13. washeluting with CH2Cl2 (100%)
  14. customThe resulting fraction was dried under vacuum
  15. customtriturated with CH2Cl2/hexanes
  16. customthe solid formed
  17. filtrationwas filtered
  18. customdried under vacuum

Sources & evidence

ORD record
ord-126a4a0f768547a1a1e76020f56f8995
Source dataset
uspto-grants-2015_07
Patent number
US09073900B2

Reaction notes

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