Water → 1,1-dimethylethyl 7-(5-fluoro-2-{[(4-methyl-2-pyridinyl)methyl]oxy}phenyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate

HRID 879994Notes

Reaction equation

HRID 879994 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[O:9][CH2:10][C:11]1[CH:16]=[C:15]([CH3:17])[CH:14]=[CH:13][N:12]=1.CC1(C)C(C)(C)OB([C:26]2[CH:35]=[C:34]3[C:29]([CH2:30][CH2:31][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:33]3)=[CH:28][CH:27]=2)O1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.O.Cl[Pd]Cl.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.[Fe+2].C(OCC)(=O)C>[F:8][C:6]1[CH:5]=[CH:4][C:3]([O:9][CH2:10][C:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[CH:13][N:12]=2)=[C:2]([C:26]2[CH:35]=[C:34]3[C:29]([CH2:30][CH2:31][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:33]3)=[CH:28][CH:27]=2)[CH:7]=1

Participants

9

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 53302321tert-Butyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroisoquinoline-2(1H)-carboxylateHCID 70664955HCID 70664955, compound

Product 1

HCID 706649621,1-dimethylethyl 7-(5-fluoro-2-{[(4-methyl-2-pyridinyl)methyl]oxy}phenyl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
120 °C

Procedure

To a degassed mixture 2-{[(2-bromo-4-fluorophenyl)oxy]methyl}-4-methylpyridine (0.09 g), 1,1-dimethylethyl 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate (0.131 g) (for preparation see WO 2007/056710) and caesium carbonate (0.296 g) in dioxane:water (4:1, 5 ml) was added PdCl2.dppf (0.025 g). The reaction mixture was heated at 120° C. overnight. The reaction mixture was added to water and extraction was carried out with ethyl acetate. The organic layer was dried over sodium sulphate and the filtrate was concentrated in vacuo. The crude product was purified through silica, eluting with 0-12% ethyl acetate in hexane. Appropriate fractions were concentrated in vacuo to yield the title compound, 0.169 g, quantitative yield.

Workup

  1. dry with materialThe organic layer was dried over sodium sulphate
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe crude product was purified through silica
  4. washeluting with 0-12% ethyl acetate in hexane
  5. concentrationAppropriate fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-ef71828b78c3428fb0c7a8cb41f90b15
Source dataset
uspto-grants-2015_03
Patent number
US08993560B2

Reaction notes

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