Hydrochloric Acid → 2-(2,5-Difluorophenyl)-6-(4-ethoxy-2-nitrophenoxy)chroman

HRID 31267

Reaction equation

HRID 31267 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([OH:19])[CH:15]=2)[O:10]1.CC(C)([O-])C.[K+].Cl[C:27]1[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH3:35])=[CH:29][C:28]=1[N+:36]([O-:38])=[O:37].Cl>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:19][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH2:34][CH3:35])=[CH:29][C:28]=3[N+:36]([O-:38])=[O:37])[CH:15]=2)[O:10]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 2407341-Chloro-4-ethoxy-2-nitrobenzeneHCID 179785262-(2,5-Difluorophenyl)chroman-6-olHCID 23665647Potassium tert-butoxide

Product 1

HCID 179785682-(2,5-Difluorophenyl)-6-(4-ethoxy-2-nitrophenoxy)chroman

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

320 mg of 2-(2,5-Difluorophenyl)chroman-6-ol (Example 14(c)) was dissolved in dry DMF and potassium tert-butoxide (150 mg) was added. The resulting mixture was stirred for 30 minutes and 1-chloro-4-ethoxy-2-nitrobenzene (250 mg) was added. The reaction mixture was refluxed for 8 hours. After cooling to room temperature 1 M HCl-solution was added into the reaction mixture and it was extracted with ethyl acetate. The combined organic extracts were washed with water and saturated NaCl-solution. The product was purified by column chromatography using heptane-ethyl acetate (3:1) as an eluant. 1H NMR (300 MHz, CDCl3) δ: 7.43 (d, 1H, J 2.9Hz), 7.25 (m, 1H), 7.08-6.97 (m, 4H), 6.89-6.75 (m, 3H), 5.31 (d, 1H, J 9.1 Hz), 4.06 (q, 2H, J 7.0 Hz), 2.97 (m, 1H), 2.74 (m, 1H), 2.26 (m, 1H), 1.98 (m, 1H), 1.44 (t, 3H, 7.0 Hz).

Workup

  1. temperatureThe reaction mixture was refluxed for 8 hours
  2. additionwas added into the reaction mixture and it
  3. extractionwas extracted with ethyl acetate
  4. washThe combined organic extracts were washed with water and saturated NaCl-solution
  5. customThe product was purified by column chromatography

Sources & evidence

ORD record
ord-d929fbcf01484c808da1b2a8c55c12ae
Source dataset
uspto-grants-2008_09
Patent number
US07425568B2

Linked notes

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