Sodium Carbonate → Ethyl 2-(3-(5-chloro-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-methoxyphenyl)acetate

HRID 1773987Notes

Reaction equation

HRID 1773987 reaction equation
Cl.Br[C:3]1[CH:4]=[CH:5][C:6]([Cl:13])=[C:7]2[C:12]=1[CH2:11][NH:10][CH2:9][CH2:8]2.[CH2:14]([O:16][C:17](=[O:36])[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=1)[CH3:15].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CO.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:14]([O:16][C:17](=[O:36])[CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([C:3]2[CH:4]=[CH:5][C:6]([Cl:13])=[C:7]3[C:12]=2[CH2:11][NH:10][CH2:9][CH2:8]3)[CH:20]=1)[CH3:15]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 58120060[4-Methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl esterHCID 896488578-Bromo-5-chloro-1,2,3,4-tetrahydro-isoquinoline hydrochloride

Product 1

HCID 118353187Ethyl 2-(3-(5-chloro-1,2,3,4-tetrahydroisoquinolin-8-yl)-4-methoxyphenyl)acetate

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 70394911MeOH toluene waterSolvent

Procedure

To a mixture under N2 of 8-bromo-5-chloro-1,2,3,4-tetrahydro-isoquinoline hydrochloride (566 mg, 2.00 mmol, 1 eq.), [4-methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester (901 mg, 2.0 mmol, 1.00 eq) and sodium carbonate (1.06 g, 10.0 mmol, 5.00 eq.) in toluene/MeOH/water 20:4:1 (40 mL), tetrakis(triphenylphosphine) palladium (0) (116 mg, 0.1 mmol, 0.05 eq.) was added and the mixture was stirred under reflux for 18 hours. The mixture was allowed to cool to r.t. and concentrated in vacuo. The residue was partitioned between AcOEt (75 mL) and water (75 mL). The layers were separated. The org. phase was washed with sat. aq. NaCl soln. (1×50 mL), dried over MgSO4 and filtered through Celite. The filtrate was concentrated in vacuo. The residue was purified by flashmaster (column: 100 g, flow: 45 mL/min, 40 fractions of 45 mL, AcOEt+MeOH 10%) to yield the title product as an orange oil.

Workup

  1. temperatureunder reflux for 18 hours
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between AcOEt (75 mL) and water (75 mL)
  4. customThe layers were separated
  5. washphase was washed with sat. aq. NaCl soln
  6. dry with material(1×50 mL), dried over MgSO4
  7. filtrationfiltered through Celite
  8. concentrationThe filtrate was concentrated in vacuo
  9. customThe residue was purified by flashmaster (column: 100 g, flow: 45 mL/min, 40 fractions of 45 mL, AcOEt+MeOH 10%)

Sources & evidence

ORD record
ord-785df3d9fb454481881b6723d7d6ec28
Source dataset
uspto-grants-2016_02
Patent number
US09255090B2

Reaction notes

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