Diisopropylethylamine → Ethyl 8-bromo-6-chloro-7-(4-(6-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylate

HRID 1626459Notes

Reaction equation

HRID 1626459 reaction equation
[Br:1][C:2]1[C:3]([O:18][C:19]2[CH:27]=[CH:26][C:22]([C:23]([OH:25])=O)=[CH:21][CH:20]=2)=[C:4]([Cl:17])[CH:5]=[C:6]2[C:11]=1[O:10][CH2:9][CH2:8][CH:7]2[C:12]([O:14][CH2:15][CH3:16])=[O:13].Cl.[Cl:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]2[N:41]=[C:40]([NH2:42])[CH:39]=[CH:38][CH:37]=2)=[CH:32][CH:31]=1.C(N(CC)C(C)C)(C)C>S(Cl)(Cl)=O.C(OCC)(=O)C.Cl>[Br:1][C:2]1[C:3]([O:18][C:19]2[CH:20]=[CH:21][C:22]([C:23](=[O:25])[NH:42][C:40]3[CH:39]=[CH:38][CH:37]=[C:36]([C:33]4[CH:34]=[CH:35][C:30]([Cl:29])=[CH:31][CH:32]=4)[N:41]=3)=[CH:26][CH:27]=2)=[C:4]([Cl:17])[CH:5]=[C:6]2[C:11]=1[O:10][CH2:9][CH2:8][CH:7]2[C:12]([O:14][CH2:15][CH3:16])=[O:13]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 670804834-(8-Bromo-6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acidHCID 672887096-(4-Chlorophenyl)pyridin-2-amine hydrochloride

Product 1

HCID 67287788Ethyl 8-bromo-6-chloro-7-(4-(6-(4-chlorophenyl)pyridin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylateYield 58.4%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolventHCID 24386Thionyl ChlorideSolvent

Procedure

A solution of 4-(8-bromo-6-chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (0.18 g, 0.40 mmol) in thionyl chloride (5 mL) was stirred and heated to gentle reflux for 30 minutes. The solution was cooled to ambient temperature and concentrated. The residual light yellow solid was dissolved in dichloromethane (4 mL). To the resulting stirred solution at ambient temperature was added 6-(4-chlorophenyl)pyridin-2-amine hydrochloride (96.6 mg, 0.40 mmol), followed by N,N-diisopropylethylamine (0.28 mL, 1.60 mmol). A solution formed, and stirring was continued at ambient temperature for 3 hours. The solution was diluted with ethyl acetate (20 mL) and 1M hydrochloric acid (10 mL), then transferred to a separatory funnel. After shaking, the organic layer was washed successively with 10 mL portions of water, 10% sodium carbonate, and brine, dried over sodium sulfate and evaporated. The residual oil was purified by chromatography on silica gel, eluting with 80/20 hexanes/ethyl acetate, to afford the desired compound as a colorless oil (0.15 g, 58% yield).

Workup

  1. temperatureheated
  2. temperatureto gentle reflux for 30 minutes
  3. concentrationconcentrated
  4. dissolutionThe residual light yellow solid was dissolved in dichloromethane (4 mL)
  5. customA solution formed
  6. stirringstirring
  7. customtransferred to a separatory funnel
  8. stirringAfter shaking
  9. washthe organic layer was washed successively with 10 mL portions of water, 10% sodium carbonate, and brine
  10. dry with materialdried over sodium sulfate
  11. customevaporated
  12. customThe residual oil was purified by chromatography on silica gel
  13. washeluting with 80/20 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-f937d8121b764c35be6c47286dc3a066
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

Loading…