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

HRID 1051448Notes

Reaction equation

HRID 1051448 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[O:5][CH2:6][CH:7]([OH:19])[CH2:8][N:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10]1.[C:23]1(B(O)O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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]>[C:2]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:22]=[CH:21][CH:20]=[C:4]([O:5][CH2:6][CH:7]([OH:19])[CH2:8][N:9]2[CH2:18][CH2:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH2:10]2)[CH:3]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 429098461-(3-bromophenoxy)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol

Product 1

HCID 867292331-([1,1'-biphenyl]-3-yloxy)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-olYield 30%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1-(3-bromophenoxy)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol (300 mg, 0.828 mmol) in dioxane (4 ml) and H2O (1 mL) was added phenylboronic acid (151.5 mg, 1.24 mmol), Pd(dppf)Cl2 (30.3 mg, 0.041 mmol) and K2CO3 (343.4 mg, 2.484 mmol) at 6° C. The reaction mixture was stirred for 16 h at 80° C. It was concentrated to remove the solvents and the residue was dissolved in ethyl acetate, washed with water. The separated organic layer was concentrated and the crude product purified by HPLC separation to give the title compound (89 mg, 30.0%) as a white solid. 1HNMR(CH3OD, 400 MHz) δ: 8.47 (br, 1H), 7.60-7.62 (m, 2H), 7.40-7.46 (m, 2H), 7.33-7.38 (m, 2H), 7.17-7.28 (m, 6H), 6.97-6.99 (m, 1H), 4.46-4.50 (m, 1H), 4.35 (s, 2H), 4.12 (d, J=2.6, 2H), 3.47-3.50 (m, 2H), 3.26-3.37 (m, 2H), 3.16 (s, 2H). LCMS (m/z): 360.2 [M+H]+

Workup

  1. concentrationIt was concentrated
  2. customto remove the solvents
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. washwashed with water
  5. concentrationThe separated organic layer was concentrated
  6. customthe crude product purified by HPLC separation

Sources & evidence

ORD record
ord-a7f6c98ae926446facc1ffb37b564963
Source dataset
uspto-grants-2016_07
Patent number
US09388173B2

Reaction notes

Loading…