Potassium Carbonate → HCID 11639093, compound

HRID 272849Notes

Reaction equation

HRID 272849 reaction equation
[CH3:1][N:2]([CH2:4][C:5]1([C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=2)[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)[CH3:3].Br[CH2:19][CH2:20][CH2:21][CH2:22]Cl.C([O-])([O-])=O.[K+].[K+].[NH:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1>CCO.CN(C=O)C>[CH3:3][N:2]([CH3:1])[CH2:4][C:5]1([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:19][CH2:20][CH2:21][CH2:22][N:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)=[CH:13][CH:12]=2)[CH2:6][CH2:7][O:8][CH2:9][CH2:10]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 31268PyrrolidineHCID 813641-Bromo-4-chlorobutaneHCID 230916214-(4-Dimethylaminomethyl-tetrahydro-pyran-4-yl)-phenol

Product 1

HCID 11639093HCID 11639093, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

4-(4-Dimethylaminomethyl-tetrahydro-pyran-4-yl)-phenol (1.5 g, 6.38 mmol), 1-bromo-4-chlorobutane (1.5 ml, 12.77 mmol), DMF (20 ml) and K2CO3 (3.5 g, 25.53 mmol) were reacted together according to general procedure B. Purification of a fraction of the crude (900 mg) by chromatography on alumina, eluant ethyl acetate:heptanes (12:88) provided a mixture of bromo and chloro phenoxy ether (220 mg) which was used in the next stage. The purified mixture (220 mg, 0.68 mmol) and pyrrolidine (0.17 ml, 2.03 mmol) were refluxed in EtOH (3 ml, 15 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 (3×5 mL). The combined ethyl acetate layers were washed with brine (3×5 ml), dired over MgSO4, filtered, washed with ethyl acetate and concentrated in vacuo. Purification by chromatography on silica, eluant 95:3:2 (DCM:MeOH:NH3) followed by a second column eluting with DCM:MeOH:NH3 (96.5:3:0.5), gave the title compound as a colourless oil (134 mg, 55%). 1H NMR (400 MHz, CDCl3) δ7.21 (d, 2H), 6.86 (d, 2H), 3.97 (t, 2H), 3.75 (dt, 2H), 3.59-3.50 (m, 2H), 2.57-2.45 (m, 6H), 2.40 (s, 2H), 2.14-2.05 (m, 2H), 1.96 (s, 6H), 1.92-1.65 (m, 10H).

Workup

  1. customPurification of a fraction of the crude (900 mg) by chromatography on alumina, eluant ethyl acetate:heptanes (12:88)
  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 (3×5 mL)
  6. washThe combined ethyl acetate layers were washed with brine (3×5 ml), dired over MgSO4
  7. filtrationfiltered
  8. washwashed with ethyl acetate
  9. concentrationconcentrated in vacuo
  10. customPurification by chromatography on silica, eluant 95:3:2 (DCM:MeOH:NH3)
  11. washeluting with DCM:MeOH:NH3 (96.5:3:0.5)

Sources & evidence

ORD record
ord-04e558639839463fbcc9a523cc21c8dc
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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