2-Fluoro-4-nitrophenol → 1-(2-(6-(7-(2-Fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)ethyl)pyrrolidin-2-one

HRID 1400907Notes

Reaction equation

HRID 1400907 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[N:16]=[CH:15][C:14]([CH2:17][CH2:18][N:19]4[CH2:23][CH2:22][CH2:21][C:20]4=[O:24])=[CH:13][CH:12]=3)[S:10][C:3]=12.[F:25][C:26]1[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[CH:29]=[CH:28][C:27]=1[OH:35].C(=O)([O-])[O-].[K+].[K+]>C1(OC2C=CC=CC=2)C=CC=CC=1>[F:25][C:26]1[CH:31]=[C:30]([N+:32]([O-:34])=[O:33])[CH:29]=[CH:28][C:27]=1[O:35][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]3[N:16]=[CH:15][C:14]([CH2:17][CH2:18][N:19]4[CH2:23][CH2:22][CH2:21][C:20]4=[O:24])=[CH:13][CH:12]=3)[S:10][C:3]=12

Participants

5

Reactant 3

HCID 98252-Fluoro-4-nitrophenol2×HCID 11430Potassium Carbonate2×HCID 584746401-(2-(6-(7-Chlorothieno[3,2-b]pyridin-2-yl)pyridin-3-yl)ethyl)pyrrolidin-2-one

Product 1

HCID 584745171-(2-(6-(7-(2-Fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl)pyridin-3-yl)ethyl)pyrrolidin-2-oneYield 47%

Reagents, catalysts & solvents 1

HCID 7583Diphenyl EtherSolvent

Conditions

Temperature
200 °C

Procedure

To chlorothienopyridine 292 (1.2 g, 3.4 mmol) in diphenyl ether (20 mL) was added 2-fluoro-4-nitrophenol (1.58 g, 10.1 mmol) and potassium carbonate (2.32 g, 16.8 mmol) and the resultant mixture was heated to 200° C. for 10 h. Extra 2-fluoro-4-nitrophenol (1.58 g, 10.1 mmol) and potassium carbonate (2.32 g, 16.8 mmol) were added and the mixture was heated at 200° C. for a further 6 h. The mixture was cooled to RT, partitioned between ethyl acetate and 1M aqueous NaOH then filtered through celite. The organic phase was collected, washed with water and brine, dried (anhydrous MgSO4), filtered and concentrated. The residue was purified by silica gel chromatography (10% methanol/ethyl acetate) to afford title compound 293 (0.76 g, 47% yield), contaminated with ˜10% starting material 292, as a yellow solid. MS (M+H): 479.5

Workup

  1. temperatureThe mixture was cooled to RT
  2. custompartitioned between ethyl acetate and 1M aqueous NaOH
  3. filtrationthen filtered through celite
  4. customThe organic phase was collected
  5. washwashed with water and brine
  6. dry with materialdried (anhydrous MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography (10% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-b718626258ad469aaa983e7d8b29cab0
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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