Dimethylformamide → 4,5-Dihydropyrido[4,3-b]thieno[2,3-d]oxepine

HRID 84465Notes

Reaction equation

HRID 84465 reaction equation
I[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][C:11]1[CH:15]=[CH:14][S:13][CH:12]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[S:13]1[C:12]2[C:2]3[CH:3]=[N:4][CH:5]=[CH:6][C:7]=3[O:8][CH2:9][CH2:10][C:11]=2[CH:15]=[CH:14]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 579002113-Iodo-4-(2-(thiophen-3-yl)ethoxy)pyridine

Product 1

HCID 579001994,5-Dihydropyrido[4,3-b]thieno[2,3-d]oxepineYield 85%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

3-Iodo-4-(2-(thiophen-3-yl)ethoxy)pyridine (1.66 g, 5.00 mmol), palladium acetate (112 mg, 0.500 mmol), triphenylphosphine (262 mg, 1.00 mmol) and potassium carbonate (1.38 g, 10.0 mmol) in N,N-dimethylformamide (80 mL, 1000 mmol) were heated at 115° C. for 2 hours. The reaction mixture was concentrated and partitioned between ethyl acetate and water. The organic layer was washed with water and brine, and dried over MgSO4. The crude product was purified on a silica gel column eluting with 50% ethyl acetate in hexane to give 4,5-dihydropyrido[4,3-b]thieno[2,3-d]oxepine (yield 0.86 g, 85%). 1H NMR (400 MHz, CDCl3) δ 8.93 (s, 1H), 8.25 (d, J=5.5, 1H), 7.23 (d, J=5.2, 1H), 6.89 (dd, J=3.6, 5.3, 2H), 4.43-4.33 (m, 2H), 3.29-3.20 (m, 2H). MS (ESI+) 204.0

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between ethyl acetate and water
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over MgSO4
  5. customThe crude product was purified on a silica gel column
  6. washeluting with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-67ab0c78bf644c29823f111e1a040ba6
Source dataset
uspto-grants-2014_09
Patent number
US08846762B2

Reaction notes

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