Sodium Hydroxide → 8-Fluoro-10,11-dihydro-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one

HRID 2218756Notes

Reaction equation

HRID 2218756 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]2[N:18]=[CH:17][CH:16]=[CH:15][C:11]=2[C:12]([OH:14])=O)[CH:5]=[CH:6][CH:7]=1.[OH-].[Na+]>O>[F:1][C:2]1[CH:7]=[CH:6][C:5]2[C:12](=[O:14])[C:11]3[C:10]([CH2:9][CH2:8][C:4]=2[CH:3]=1)=[N:18][CH:17]=[CH:16][CH:15]=3

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 44203203HCID 44203203, compound

Product 1

HCID 442032048-Fluoro-10,11-dihydro-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-oneYield 81%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Combine crude 2-[2-(3-fluoro-phenyl)-ethyl]-nicotinic acid (2.06 g, 15.0 mmol) and polyphosphoric acid (100 g) and heat the mixture to 160° C. for 6 h. Allow slow cooling of the reaction mixture over 12 h, then reheat the mixture to 160° C. and pour it into ice (200 g). Complete the transfer using water and adjust the pH of the aqueous mixture to ˜8.0 with 50% aqueous sodium hydroxide solution. Extract the product with methylene chloride. Dry the combined organic extracts with magnesium sulfate, filter and concentrate. Purify the crude product via flash chromatography (25% ethyl acetate/hexanes to 50% ethyl acetate/hexanes) to provide 1.54 mg (81%) of purified product. LCMS (APCI-pos): 228.1 (M+H). 1HNMR (CDCl3, 400 MHz): δ8.63 (dd, 1H), 8.39 (dd, 1H), 8.01 (dd, 1H), 7.31 (dd, 1H), 7.02 (dt, 1H), 6.95 (dd, 1H), 3.46-3.43 (m, 2H), 3.23-3.21 (m, 2H). (Literature reference: Journal of Heterocyclic Chemistry 1971, 73).

Workup

  1. temperatureAllow slow cooling of the reaction mixture over 12 h
  2. customto 160° C.
  3. extractionExtract the product with methylene chloride
  4. dry with materialDry the combined organic extracts with magnesium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the crude product via flash chromatography (25% ethyl acetate/hexanes to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-18fa99fb3c894628a56077b15e02caf1
Source dataset
uspto-grants-2008_08
Patent number
US07411072B2

Reaction notes

Loading…