2-Bromoethyl ethyl ether → HCID 19772014, compound

HRID 1614637Notes

Reaction equation

HRID 1614637 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[CH2:23]([O:25][CH2:26][CH2:27]Br)[CH3:24].C(=O)(O)[O-].[Na+].CO.C(Cl)[Cl:37]>>[OH2:25].[ClH:37].[CH2:23]([O:25][CH2:26][CH2:27][N:13]1[CH2:14][CH2:15][CH:10]([CH:9]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)[NH:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:11][CH2:12]1)[CH3:24]

Participants

5

Reactant 4

HCID 611412-Bromoethyl ethyl etherHCID 516892Sodium BicarbonateHCID 19771957N,alpha-bis(4-fluorophenyl)-4-piperidinemethanamineHCID 21226129Dichloromethane methanol

Product 1

HCID 19772014HCID 19772014, compoundYield 39.8%

Procedure

A mixture of N,α-bis(4-fluorophenyl)-4-piperidinemethanamine (3.33 g, 0.011 mol), 2-bromoethyl ethyl ether (1.69 g, 0.011 mol), and sodium bicarbonate (1.68 g, 0.011 mol) was stirred under nitrogen 16 h at room temperature. The mixture was then heated at reflux for 4 h and stirred 16 h at room temperature. The reaction was concentrated to dryness and partitioned between chloroform and water. The chloroform layer was back extracted with 5% sodium hydroxide. The chloroform layer was dried (Na2SO4), filtered, and the chloroform was removed to give an oil. The oil was subjected to flash chromatography on silica gel using methanol-methylene chloride mixtures for elution. Fractions of similar purity were combined and solvents removed. A brown oil was obtained which crystallized to a brown solid. This material was converted to the hydrochloride salt and the salt was recrystallized from methanol-diethyl ether to give a white solid. The solid was dried 16 h in vacuo at 78° C. This process furnished 2.00 g (39.8%) of white crystalline solid mp 241°-243° C. (dec.).

Workup

  1. temperatureThe mixture was then heated
  2. temperatureat reflux for 4 h
  3. stirringstirred 16 h at room temperature
  4. concentrationThe reaction was concentrated to dryness
  5. custompartitioned between chloroform and water
  6. extractionThe chloroform layer was back extracted with 5% sodium hydroxide
  7. dry with materialThe chloroform layer was dried (Na2SO4)
  8. filtrationfiltered
  9. customthe chloroform was removed
  10. customto give an oil
  11. washfor elution
  12. customsolvents removed
  13. customA brown oil was obtained which
  14. customcrystallized to a brown solid
  15. customthe salt was recrystallized from methanol-diethyl ether
  16. customto give a white solid
  17. customThe solid was dried 16 h in vacuo at 78° C

Sources & evidence

ORD record
ord-5d8489007f65424f8c60aac5d4a26857
Source dataset
uspto-grants-1993_03
Patent number
US05198449

Reaction notes

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