3-(3-(Piperidin-1-ylmethyl)phenoxy)propan-1-amine → HCID 178516517, compound

HRID 365104Notes

Reaction equation

HRID 365104 reaction equation
[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:16]=[CH:17][CH:18]=2)[O:11][CH2:12][CH2:13][CH2:14][NH2:15])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:20]1[CH2:25][C:24](=[O:26])[CH:23]=[CH:22][N:21]=1>Cl>[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:16]=[CH:17][CH:18]=2)[O:11][CH2:12][CH2:13][CH2:14][NH:15][C:22]2[CH2:23][C:24](=[O:26])[CH:25]=[CH:20][N:21]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 102205613-(3-(Piperidin-1-ylmethyl)phenoxy)propan-1-amineHCID 70416330HCID 70416330, compound

Product 1

HCID 178516517HCID 178516517, compoundYield 58.8%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

3-[3-(Piperidinomethyl)phenoxy]propylamine (14.84 g) and 2-bromopyrid-4-one (5.20 g) were stirred together at 165°-170° C. for 4 hours. The reaction mixture was cooled to give a dark orange glassy solid which was dissolved in 2N hydrochloric acid to give a solution having a pH of 4.5. This solution was washed thoroughly with diethyl ether (8×) and chloroform (4×) to remove residual 2-bromopyrid-4-one and some by-product. The aqueous phase was taken to pH 9-10 with 2N sodium hydroxide and extracted into chloroform (9×). The chloroform extracts were combined, dried and evaporated under reduced pressure to afford a dark orange oil. This oil was subjected to medium pressure column chromatography on silica gel using gradient elution; ethyl acetate→10% methanol:90% ethyl acetate. The desired fractions were collected, combined and evaporated under reduced pressure to give the title compound (6.0 g) as a yellow-orange oil which was washed with diethyl ether.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customto give a dark orange glassy solid which
  3. customto give a solution
  4. washThis solution was washed thoroughly with diethyl ether (8×) and chloroform (4×)
  5. customto remove residual 2-bromopyrid-4-one
  6. extractionextracted into chloroform (9×)
  7. customdried
  8. customevaporated under reduced pressure
  9. customto afford a dark orange oil
  10. washThis oil was subjected to medium pressure column chromatography on silica gel using gradient elution
  11. customThe desired fractions were collected
  12. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-d99d6e28c02c4277a9d27f74dcf22c63
Source dataset
uspto-grants-1986_08
Patent number
US04608380

Reaction notes

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