Potassium Carbonate → 1-((5'-chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)oxy)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol

HRID 1051481Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1051481
[CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][N:2]1[CH2:11][CH:12]([OH:30])[CH2:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17](B2OC(C)(C)C(C)(C)O2)[CH:16]=1.Br[C:32]1[CH:37]=[C:36]([Cl:38])[CH:35]=[CH:34][C:33]=1[O:39][CH3:40].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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]>[Cl:38][C:36]1[CH:35]=[CH:34][C:33]([O:39][CH3:40])=[C:32]([C:17]2[CH:18]=[CH:19][CH:20]=[C:15]([O:14][CH2:13][CH:12]([OH:30])[CH2:11][N:2]3[CH2:3][CH2:4][C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[CH2:1]3)[CH:16]=2)[CH:37]=1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 5219352-Bromo-4-chloroanisoleHCID 867292361-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-2-ol

Produkt 1

HCID 867292621-((5'-chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)oxy)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-olAusbeute 39,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a solution of 1-(3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-2-ol (250 mg, 0.61 mmol) in Dioxane (3 mL) was added 2-bromo-4-chloro-1-methoxybenzene (135 mg, 0.61 mmol), 2N K2CO3 (1 mL, 2 mmol) and PdCl2(dppf)2 (20 mg, 0.025 mmol). The reaction mixture was heated at 120° C. under microwave conditions for 30 minutes before being concentrated to remove the solvents. The residue was dissolved in ethyl acetate, washed with water and the separated organic layer was dried and concentrated to yield a crude product which was purified by HPLC separation to give the title compound (102 mg, 39.5%). 1HNMR (CH3OD, 400 MHz) δ: 7.36-7.28 (m, 7H), 7.10-7.02 (m, 3H), 6.98-6.90 (m, 1H), 4.69-4.48 (m, 4H), 4.12-4.03 (m, 2H), 3.78 (s, 3H), 3.70-3.64 (m, 1H), 3.52-3.42 (m, 2H), 3.29-3.18 (m, 2H). LCMS (m/z): 424.2 [M+H]+

Aufarbeitung

  1. concentrationbefore being concentrated
  2. customto remove the solvents
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed with water
  5. customthe separated organic layer was dried
  6. concentrationconcentrated
  7. customto yield a crude product which
  8. customwas purified by HPLC separation

Quellen und Nachweise

ORD-Eintrag
ord-13b747d4c8494cff8b04f48e562585d7
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09388173B2

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