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

HRID 1935786Notes

Reaction equation

HRID 1935786 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.[CH2:18]([O:20][C:21](=[O:31])[CH2:22][C:23]1[CH:28]=[CH:27][C:26](I)=[CH:25][C:24]=1[F:30])[CH3:19].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>[CH2:18]([O:20][C:21](=[O:31])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([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:25][C:24]=1[F:30])[CH3:19]

Participants

9

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 18740710Ethyl 2-fluoro-4-iodophenylacetate2×HCID 225689952-Cyclopropyl-6-ethynyl-4,4-dimethyl-1,2,3,4-tetrahydroisoquinoline2×

Product 1

HCID 69548286[4-(2-Cyclopropyl-4,4-dimethyl-1,2,3,4-tetrahydro-isoquinolin-6-ylethynyl)-2-fluoro-phenyl]-acetic acid ethyl esterYield 47.4%

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-6-ethynyl-4,4-dimethyl-1,2,3,4-tetrahydro-isoquinoline(Intermediate 27, 0.13 g, 0.571 mmol), 2-fluoro-4-iodo phenyl acetic acid ethyl ester (Reagent C, 0.16 g, 0.52 mmol), triethyl amine (0.8 mL), anhydrous tetrahydrofuran (2 mL), copper(I)iodide (0.051 g, 0.27 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.1 g, 0.1 4 mmol) followed by flash column chromatography over silica gel (230-400 mesh) using 10% ethyl acetate in hexane as the eluent, 0.1 g 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 (0.055 g, 24%).

Sources & evidence

ORD record
ord-90a417eae0204b319d8cefc755fb2fca
Source dataset
uspto-grants-2002_05
Patent number
US06387892B1

Reaction notes

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