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Water → 5-Benzyl-6-(piperidin-4-yloxy)-isoquinoline

HRID 1022868
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HRID 1022868 반응식
O.C(OC([N:9]1[CH2:14][CH2:13][CH:12]([O:15][C:16]2[C:17](Br)=[C:18]3[C:23](=[CH:24][CH:25]=2)[CH:22]=[N:21][CH:20]=[CH:19]3)[CH2:11][CH2:10]1)=O)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:33]([B-](F)(F)F)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.[K+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:33]([C:17]1[C:16]([O:15][CH:12]2[CH2:11][CH2:10][NH:9][CH2:14][CH2:13]2)=[CH:25][CH:24]=[C:23]2[C:18]=1[CH:19]=[CH:20][N:21]=[CH:22]2)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 23692459Potassium benzyltrifluoroboranuideHCID 576469744-(5-Bromo-isoquinolin-6-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 576469395-Benzyl-6-(piperidin-4-yloxy)-isoquinoline수율 5.5%

시약·촉매·용매 2

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
촉매
HCID 8028Tetrahydrofuran용매

실험 절차

0.3 mL of water were added to a solution of 81 mg (0.2 mmol) of 4-(5-bromo-isoquinoline-6-yloxy)-piperidin-1-carboxylic acid tert-butyl ester (11), 195 mg (0.6 mmol) of Cs2CO3, 14.6 mg (0.02 mmol) of Pd(dppf)Cl2 and 51 mg (0.26 mmol) of potassium benzyltrifluoroborate in 3 mL of THF. Argon was bubbled through the mixture for 10 minutes and then the reaction was heated to reflux for 16 h (incomplete conversion). After cooling to room temperature water and ethyl acetate were added. The organic layer was separated, dried over Na2SO4. After removal of the solvents 2 mL 5-6 N HCl in isopropanol was added. After 2 h the solvents were distilled off and the remainder was subjected twice to preparative HPLC to give 3.5 mg compound 29 as trifluoroacetate.

후처리

  1. customArgon was bubbled through the mixture for 10 minutes
  2. temperaturethe reaction was heated
  3. temperatureto reflux for 16 h (incomplete conversion)
  4. additionwere added
  5. customThe organic layer was separated
  6. dry with materialdried over Na2SO4
  7. customAfter removal of the solvents 2 mL 5-6 N HCl in isopropanol
  8. additionwas added
  9. distillationAfter 2 h the solvents were distilled off

출처 및 근거

ORD 기록
ord-27994516d3ac41088d1c5f6cc59732a3
출처 데이터셋
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08722671B2

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