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

HRID 1051481Notes

Reaction equation

HRID 1051481 reaction equation
[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

Participants

6

Reactant 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

Product 1

HCID 867292621-((5'-chloro-2'-methoxy-[1,1'-biphenyl]-3-yl)oxy)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-olYield 39.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

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]+

Workup

  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

Sources & evidence

ORD record
ord-13b747d4c8494cff8b04f48e562585d7
Source dataset
uspto-grants-2016_07
Patent number
US09388173B2

Reaction notes

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