Potassium Carbonate → HCID 68576107, compound

HRID 272919Notes

Reaction equation

HRID 272919 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Br[CH2:17][CH2:18][CH2:19][CH2:20]Cl.[C:22]([O-])([O-])=O.[K+].[K+].[NH:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1>CCO.CN(C=O)C>[N:28]1([CH2:29][CH2:30][CH2:31][CH2:32][CH2:22][O:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]3([C:14]#[N:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[CH2:20][CH2:19][CH2:18][CH2:17]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 31268PyrrolidineHCID 813641-Bromo-4-chlorobutaneHCID 230916094-(4-Hydroxy-phenyl)-tetrahydro-pyran-4-carbonitrile

Product 1

HCID 68576107HCID 68576107, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

4-(4-Hydroxy-phenyl)-tetrahydro-pyran-4-carbonitrile (1.5 g, 7.39 mmol), 1-bromo-4-chlorobutane (1.7 ml, 14.77 mmol), DMF (20 ml) and K2CO3 (4.1 g, 29.56 mmol) were reacted together according to general procedure E. Purification by chromatography on silica, eluant ethyl acetate:heptanes (33:66) provided a mixture of bromo and chloro phenoxy ether (1.3 g, 60%) which was used in the next stage. A portion of the mixture (0.5 g, 1.70 mmol) and pyrrolidine (0.42 ml, 5.11 mmol) were refluxed in EtOH (5 ml, 10 vol) overnight. The reaction was concentrated in vacuo and partitioned between 2M NaOH (10 ml) and ethyl acetate (10 ml). The aqueous was extracted with ethyl acetate (3×10 mL). The combined ethyl acetate layers were washed with brine (3×10 ml), dried over MgSO4, filtered, washed with ethyl acetate and concentrated in vacuo. Purification by chromatography on silica, eluant DCM:MeOH:NH3 (95:4:1) increasing gradually to DCM:MeOH:NH3 (93:6:1), gave the title compound as a pale yellow solid (350 mg, 63%). 1H NMR (400 MHz, DMSO-d6) δ 7.38 (d, 2H), 6.92 (d, 2H), 4.11-4.03 (m, 2H), 3.99 (t, 2H), 3.89 (td, 2H), 2.58-2.43 (m, 6H), 2.15-1.99 (m, 4H), 1.89-1.64 (m, 8H).

Workup

  1. customPurification by chromatography on silica, eluant ethyl acetate:heptanes (33:66)
  2. customprovided
  3. concentrationThe reaction was concentrated in vacuo
  4. custompartitioned between 2M NaOH (10 ml) and ethyl acetate (10 ml)
  5. extractionThe aqueous was extracted with ethyl acetate (3×10 mL)
  6. washThe combined ethyl acetate layers were washed with brine (3×10 ml)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. washwashed with ethyl acetate
  10. concentrationconcentrated in vacuo
  11. customPurification by chromatography on silica, eluant DCM:MeOH:NH3 (95:4:1)
  12. temperatureincreasing gradually to DCM:MeOH:NH3 (93:6:1)

Sources & evidence

ORD record
ord-01f98a7d666f49f0999ebbbc7e43428e
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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