Triethylamine → HCID 71258840, compound

HRID 1424830Notes

Reaction equation

HRID 1424830 reaction equation
CCN(CC)CC.[Br:8][C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][C:10]=1[Cl:18].[NH2:19][C:20]1[C:40]([CH:41]2[CH2:43][CH2:42]2)=[CH:39][C:23]2[C:24]([C:34]([O:36][CH2:37][CH3:38])=[O:35])=[C:25]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)[O:26][C:22]=2[CH:21]=1.CCOC(C)=O>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:8][C:9]1[CH:14]=[CH:13][C:12]([NH:19][C:20]2[C:40]([CH:41]3[CH2:43][CH2:42]3)=[CH:39][C:23]3[C:24]([C:34]([O:36][CH2:37][CH3:38])=[O:35])=[C:25]([C:27]4[CH:28]=[CH:29][C:30]([Cl:33])=[CH:31][CH:32]=4)[O:26][C:22]=3[CH:21]=2)=[CH:11][C:10]=1[Cl:18]

Participants

7

Reactant 4

HCID 8471Triethylamine4×HCID 8857Ethyl AcetateHCID 46739822(4-Bromo-3-chlorophenyl)boronic acid3×HCID 67354469HCID 67354469, compound

Product 1

HCID 71258840HCID 71258840, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalyst3×HCID 6344DichloromethaneSolvent4×

Procedure

NEt3 (0.490 mL, 3.51 mmol) was added to a suspension of (4-bromo-3-chlorophenyl)boronic acid (364 mg, 1.546 mmol) in DCM (7 mL) and the resulting solution was added dropwise to mixture of ethyl 6-amino-2-(4-chlorophenyl)-5-cyclopropylbenzofuran-3-carboxylate (500 mg, 1.405 mmol), copper(II) acetate (281 mg, 1.546 mmol), 3 Å molecular sieves (1 g) and NEt3 (0.490 mL, 3.51 mmol) in DCM (7 mL) stirring vigorously at RT open to the air in a flask equipped with a drying tube. After stirring for 4 h at RT, another solution of NEt3 (0.490 mL, 3.51 mmol) and (4-bromo-3-chlorophenyl)boronic acid (364 mg, 1.546 mmol) in DCM (7 mL) was added dropwise to the reaction mixture, followed by more copper(II) acetate (281 mg, 1.546 mmol). The reaction mixture was stirred for 3 d and more solution of NEt3 (0.490 mL, 3.51 mmol) and (4-bromo-3-chlorophenyl)boronic acid (364 mg, 1.546 mmol) in DCM (7 mL) was added dropwise with further addition of copper(II) acetate (281 mg, 1.546 mmol). After 2 h, EtOAc was added followed by Celite. The mixture was stirred for 30 min then filtered through a pad of Celite and the brown solution was concentrated to dryness. EtOAc was added followed by water. The organic layer was separated, washed with water, brine, dried over MgSO4, filtered and concentrated. The crude product was purified on silica gel (hex/EtOAc) to give ethyl 6-((4-bromo-3-chlorophenyl)amino)-2-(4-chlorophenyl)-5-cyclopropylbenzofuran-3-carboxylate (685 mg, 1.231 mmol, 88% yield) as an orange foam. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.17 (s, 1H), 7.98-8.07 (m, 2H), 7.58-7.65 (m, 3H), 7.49-7.56 (m, 2H), 7.11 (d, 1H), 6.87 (dd, 1H), 4.36 (q, 2H), 1.95-2.12 (m, 1H), 1.36 (t, 3H), 0.93-1.05 (m, 2H), 0.57-0.71 (m, 2H).

Workup

  1. customequipped with a drying tube
  2. stirringAfter stirring for 4 h at RT
  3. stirringThe reaction mixture was stirred for 3 d
  4. stirringThe mixture was stirred for 30 min
  5. filtrationthen filtered through a pad of Celite
  6. concentrationthe brown solution was concentrated to dryness
  7. additionEtOAc was added
  8. customThe organic layer was separated
  9. washwashed with water, brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude product was purified on silica gel (hex/EtOAc)

Sources & evidence

ORD record
ord-cc116782f33942e9b65485691ebb8db6
Source dataset
uspto-grants-2015_01
Patent number
US08927593B2

Reaction notes

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