Trifluoroacetic acid → 4-(1-Piperazinyl)isoquinoline

HRID 1935463노트

반응식

HRID 1935463 반응식
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[N:4][CH:3]=1.[N:12]1(C(OC(C)(C)C)=O)[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+].FC(F)(F)C(O)=O>ClCCl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[N:12]1([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:5]=[N:4][CH:3]=2)[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1

참가 물질

9

반응물 5

HCID 6422Trifluoroacetic acidHCID 737434-BromoisoquinolineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxide

생성물 1

HCID 117698304-(1-Piperazinyl)isoquinoline

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 6344Dichloromethane용매

반응 조건

온도
75 °C

실험 절차

4.51 g (21.7 mmol) of 4-bromoisoquinoline, 4.65 g (25.0 mmol) of t-butyl piperazine-N-carboxylate, 0.1 g (0.11 mmol) of tris(dibenzylideneacetone)dipalladium, 0.11 g (0.18 mmol) of 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl and 2.92 g (30.4 mmol) of sodium t-butoxide were together added to 50 ml of toluene and the mixture was stirred at 75° C. for 2 h. The reaction mixture was added to ice/sodium chloride and the latter mixture was extracted with ethyl acetate; the organic phase was dried over sodium sulfate and the solvent was removed on a rotary evaporator. The product crystallized out and was filtered off with suction and washed with pentane. This resulted in 5.5 g (81%) of the Boc-protected piperazine (m.p.: 111° C.). 5.2 g (16.6 mmol) of this substance were taken up in 17 ml of dichloromethane, after which 17 ml (0.22 mmol) of trifluoroacetic acid were slowly added at 0° C. The mixture was left to stir at 0° C. for 4 h and was then poured onto ice water and this latter mixture was extracted with dichloromethane. The aqueous phase was filtered, rendered alkaline and extracted with dichloromethane. After drying over sodium sulfate and to a large extent removing the solvent, dilution was carried out with diethyl ether, and the hydrochloride was precipitated with ethereal hydrochloric acid. This afforded 3.2 g (67%) of the product having a m.p. of 293-294° C.

후처리

  1. extractionthe latter mixture was extracted with ethyl acetate
  2. dry with materialthe organic phase was dried over sodium sulfate
  3. customthe solvent was removed on a rotary evaporator
  4. customThe product crystallized out
  5. filtrationwas filtered off with suction
  6. washwashed with pentane
  7. customThis resulted in 5.5 g (81%) of the Boc-protected piperazine (m.p.: 111° C.)
  8. waitThe mixture was left
  9. stirringto stir at 0° C. for 4 h
  10. additionwas then poured onto ice water
  11. extractionthis latter mixture was extracted with dichloromethane
  12. filtrationThe aqueous phase was filtered
  13. extractionextracted with dichloromethane
  14. dry with materialAfter drying over sodium sulfate and to a large extent
  15. customremoving the solvent, dilution
  16. customthe hydrochloride was precipitated with ethereal hydrochloric acid

출처 및 근거

ORD 기록
ord-88901ed212334828a7b7fb2b76bdde6e
출처 데이터셋
uspto-grants-2002_05
특허 번호
US06387912B1

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