Tetrahydrofuran → [4-(2-Cyclopropyl-4,4-dimethyl-1,2,3,4-tetrahydro-isoquinolin-6ylethynyl)-phenyl]-acetic acid methyl ester

HRID 395045Notes

Reaction equation

HRID 395045 reaction equation
[CH:1]1([N:4]2[CH2:13][C:12]([CH3:15])([CH3:14])[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([C:16]#[CH:17])[CH:10]=3)[CH2:5]2)[CH2:3][CH2:2]1.[CH3:18][O:19][C:20](=[O:29])[CH2:21][C:22]1[CH:27]=[CH:26][C:25](I)=[CH:24][CH:23]=1.C(N(CC)CC)C.O1CCCC1>CCCCCC.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C>[CH3:18][O:19][C:20](=[O:29])[CH2:21][C:22]1[CH:23]=[CH:24][C:25]([C:17]#[C:16][C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[CH2:5][N:4]([CH:1]2[CH2:3][CH2:2]2)[CH2:13][C:12]3([CH3:14])[CH3:15])=[CH:26][CH:27]=1

Participants

9

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 10378700Methyl 4-Iodophenylacetate2×HCID 225689952-Cyclopropyl-6-ethynyl-4,4-dimethyl-1,2,3,4-tetrahydroisoquinoline2×

Product 1

HCID 69548441[4-(2-Cyclopropyl-4,4-dimethyl-1,2,3,4-tetrahydro-isoquinolin-6ylethynyl)-phenyl]-acetic acid methyl esterYield 23.4%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Following general procedure F and using 2-cyclopropyl-4,4-dimethyl-6-ethynyl -1,2,3,4-tetrahydro-isoquinoline(Intermediate 27, 0.13 g, 0.571 mmol), 4-iodo phenyl acetic acid methyl ester (Reagent B, 0.16 g, 0.58 mmol), triethyl amine (0.5 mL), anhydrous tetrahydrofuran (2 mL), copper(I)iodide (0.04 g, 0.21 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.12 g, 0.17 mmol) followed by flash column chromatography over silica gel (230-400 mesh) using 10% ethyl acetate in hexane as the eluent, 0.05g of the title compound was obtained as an oil. It was further purified by preparative normal phase HPLC on a partisil-10 silica column using 10% ethyl acetate in hexane as the mobile phase (0.01 g, 6%).

Sources & evidence

ORD record
ord-d24b8cd50b1c43fc8b434800e9a6096a
Source dataset
uspto-grants-2003_08
Patent number
US06603019B2

Reaction notes

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