2-Fluoro-4-nitrophenol → 2-(5-(1,3-Dioxan-2-yl)pyridin-2-yl)-7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridine

HRID 1401320Notes

Reaction equation

HRID 1401320 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[CH:8]=[CH:9][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3Cl)[CH:14]=2)=[N:11][CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+].[N+:29]([C:32]1[CH:37]=[CH:36][C:35]([OH:38])=[C:34]([F:39])[CH:33]=1)([O-:31])=[O:30]>C1(OC2C=CC=CC=2)C=CC=CC=1.C(Cl)Cl>[O:1]1[CH2:6][CH2:5][CH2:4][O:3][CH:2]1[C:7]1[CH:8]=[CH:9][C:10]([C:13]2[S:21][C:20]3[C:15](=[N:16][CH:17]=[CH:18][C:19]=3[O:38][C:35]3[CH:36]=[CH:37][C:32]([N+:29]([O-:31])=[O:30])=[CH:33][C:34]=3[F:39])[CH:14]=2)=[N:11][CH:12]=1

Participants

6

Reactant 3

HCID 98252-Fluoro-4-nitrophenolHCID 10340Sodium CarbonateHCID 579672702-(5-(1,3-Dioxan-2-yl)pyridin-2-yl)-7-chlorothieno[3,2-b]pyridine

Product 1

HCID 252122432-(5-(1,3-Dioxan-2-yl)pyridin-2-yl)-7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridineYield 82.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 7583Diphenyl EtherSolvent

Conditions

Temperature
180 °C

Procedure

To a suspension of 29 (22.48 g, 67.5 mmol) in phenyl ether (65 mL) was added sodium carbonate (14.32 g, 135 mmol) and 2-fluoro-4-nitrophenol (3) (15.92 g, 101 mmol). The reaction mixture was heated at 180° C. for 2 h, cooled down to 40° C., diluted with DCM (300 mL), stirred at r.t. for 15 min and filtered. The filtrate was collected and concentrated to a minimal volume; Et2O (200 mL) was added and the formed suspension was stirred for 30 min. The solid material was collected by filtration, to afford intermediate 30 (25.20 g, 55.6 mmol, 82% yield) as a beige solid. 1H NMR (400 MHz, DMSO-d) δ (ppm): 8.63-8.62 (m, 2H), 8.48 (dd, J=10.6, 2.6 Hz, 1H), 8.43 (s, 1H), 8.31 (d, J=8.0 Hz, 1H), 8.21 (dt, J=8.8, 1.2 Hz, 1H), 7.94 (dd, J=8.4, 2.0 Hz, 1H), 7.71 (t, J=8.6 Hz, 1H), 6.98 (d, J=5.2 Hz, 1H), 5.67 (s, 1H), 4.19 (dd, J=10.8, 5.2 Hz, 2H), 3.98 (td, J=12.0, 2.0 Hz, 2H), 2.08-1.99 (m, 1H), 1.46 (d, J=13.6 Hz, 1H). MS (m/z): 454.2 (M+H).

Workup

  1. temperaturecooled down to 40° C.
  2. filtrationfiltered
  3. customThe filtrate was collected
  4. concentrationconcentrated to a minimal volume
  5. additionEt2O (200 mL) was added
  6. stirringthe formed suspension was stirred for 30 min
  7. filtrationThe solid material was collected by filtration

Sources & evidence

ORD record
ord-061b098236e74544bb5eaae25943dc9c
Source dataset
uspto-grants-2014_12
Patent number
US08907091B2

Reaction notes

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