Potassium Carbonate → 8-(4-tert-Butoxycarbonylmethyl-2-isopropoxy-phenyl)-5-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

HRID 1773984Notes

Reaction equation

HRID 1773984 reaction equation
[C:1]([O:5][C:6](=[O:19])[CH2:7][C:8]1[CH:13]=[CH:12][C:11](Cl)=[C:10]([O:15][CH:16]([CH3:18])[CH3:17])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:20]([O:27][C:28]([N:30]1[CH2:39][CH2:38][C:37]2[C:32](=[C:33](B3OC(C)(C)C(C)(C)O3)[CH:34]=[CH:35][C:36]=2[F:40])[CH2:31]1)=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[CH2:20]([O:27][C:28]([N:30]1[CH2:39][CH2:38][C:37]2[C:32](=[C:33]([C:11]3[CH:12]=[CH:13][C:8]([CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:19])=[CH:9][C:10]=3[O:15][CH:16]([CH3:18])[CH3:17])[CH:34]=[CH:35][C:36]=2[F:40])[CH2:31]1)=[O:29])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 89648442Tert-butyl 2-(4-chloro-3-isopropoxyphenyl)acetateHCID 896488855-fluoro-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

Product 1

HCID 896493728-(4-tert-Butoxycarbonylmethyl-2-isopropoxy-phenyl)-5-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture under N2 of (4-chloro-3-isopropoxy-phenyl)-acetic acid tert-butyl ester (142 mg, 0.50 mmol, 1.00 eq.), 5-fluoro-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (232 mg, 0.50 mmol, 1.00 eq.), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (18 mg, 0.03 mmol, 0.05 eq.) and potassium carbonate (138 mg, 1.00 mmol, 2.00 eq.) in toluene (2.5 mL) and water (0.25 mL) was stirred at 110° C. for 2 days. The mixture was allowed to cool to r.t., filtered through celite, and concentrated in vacuo. The residue was purified by flashmaster (column: 25 g, flow: 30 mL/min, 30 fractions of 30 mL, Heptane 100% to Heptane+20% AcOEt) to yield the title compound as a pale yellow oil.

Workup

  1. filtrationfiltered through celite
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by flashmaster (column: 25 g, flow: 30 mL/min, 30 fractions of 30 mL, Heptane 100% to Heptane+20% AcOEt)

Sources & evidence

ORD record
ord-578ff72de11b441c989ccd67e3e3552d
Source dataset
uspto-grants-2016_02
Patent number
US09255090B2

Reaction notes

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