Triethylamine → (S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-hydroxyethanone

HRID 2195712Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2195712
[CH2:1]([C@@H:8]1[NH:13][CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C([O:42][CH2:43][C:44](Cl)=[O:45])C1C=CC=CC=1>C1COCC1.CCOC(C)=O.O.CO>[CH2:1]([C@H:8]1[CH2:9][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:11][CH2:12][N:13]1[C:43](=[O:42])[CH2:44][OH:45])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

8

Edukt 3

HCID 8471TriethylamineHCID 177085Benzyloxyacetyl chlorideHCID 16725642(S)-3-Benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine

Produkt 1

HCID 23627687(S)-1-(2-benzyl-4-(3-(cyclopentyloxy)-4-methoxyphenyl)piperazin-1-yl)-2-hydroxyethanoneAusbeute 18 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of (S)-3-Benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine (Example 2) (73 mg, 0.2 mmol) in THF (1.5 mL) at room temperature was treated with triethylamine (42 μL, 0.3 mmol) followed by benzyloxyacetyl chloride (19 μL, 0.2 mmol). The reaction mixture was stirred for 2 h then diluted with EtOAc (2 mL) and water (2 mL). The organic phase was isolated and further washed with an additional portion of a water (2 mL) followed by a brine solution (2 mL). The organic component was dried over MgSO4, filtered, and evaporated to an oil which was purified by silica gel flash chromatography with 20% then 40% EtOAc/hexane as eluant to afford coupled product as an oil (69 mg, 67%). LC/MS 7.64 min, [M+1]+ 515. The intermediate benzyloxy ether (60 mg, 0.117 mmol) was dissolved in MeOH (20 mL), purged with a stream of nitrogen, treated with 20% Pd/C (140 mg, 50% water content), and hydrogenated under 40 psi pressure of hydrogen for 4 h. The crude reaction mixture was then purged with nitrogen, filtered, evaporated, and purified by silica gel flash chromatography with 40% then 75% EtOAc/hexane as eluant to afford product as an oil (9 mg, 18%). LC/MS 6.55 min, [M+1]+ 425.

Aufarbeitung

  1. customThe organic phase was isolated
  2. washfurther washed with an additional portion of a water (2 mL)
  3. dry with materialThe organic component was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated to an oil which
  6. customwas purified by silica gel flash chromatography with 20%
  7. custom40% EtOAc/hexane as eluant to afford
  8. customLC/MS 7.64 min, [M+1]+ 515
  9. custompurged with a stream of nitrogen
  10. additiontreated with 20% Pd/C (140 mg, 50% water content)
  11. waithydrogenated under 40 psi pressure of hydrogen for 4 h
  12. customThe crude reaction mixture
  13. customwas then purged with nitrogen
  14. filtrationfiltered
  15. customevaporated
  16. custompurified by silica gel flash chromatography with 40%

Quellen und Nachweise

ORD-Eintrag
ord-d33c39c2b57b47bfb53993e953eb13b9
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08338405B2

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