Tetrahydrofuran → 4-[(8-Cyclopropyl-3,4-dihydro-4,4-dimethylspiro[-2H-1-benzopyran-2,1'-cyclopropane]-6-yl)ethynyl]-2-fluoro-benzeneacetic acid methyl ester

HRID 2299381Notes

Reaction equation

HRID 2299381 reaction equation
[CH:1]1([C:4]2[C:15]3[O:14][C:11]4([CH2:13][CH2:12]4)[CH2:10][C:9]([CH3:17])([CH3:16])[C:8]=3[CH:7]=[C:6]([C:18]#[CH:19])[CH:5]=2)[CH2:3][CH2:2]1.C(O[C:24]1[CH:29]=[CH:28][C:27](I)=[C:26]([CH3:31])[C:25]=1[F:32])(=O)C.C(N(CC)CC)C.O1CCCC1.[C:45]([O:48][CH2:49]C)(=[O:47])C>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>[CH3:49][O:48][C:45](=[O:47])[CH2:31][C:26]1[CH:27]=[CH:28][C:29]([C:19]#[C:18][C:6]2[CH:5]=[C:4]([CH:1]3[CH2:3][CH2:2]3)[C:15]3[O:14][C:11]4([CH2:13][CH2:12]4)[CH2:10][C:9]([CH3:16])([CH3:17])[C:8]=3[CH:7]=2)=[CH:24][C:25]=1[F:32]

Participants

9

Reactant 5

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 225689518-Cyclopropyl-6-ethynyl-3 4-dihydro-4,4-dimethylspiro[2H-1-benzopyran-2,1'-cvclopropane]2×HCID 69548383Methyl-2-fluoro-4-iodo-phenyl acetate

Product 1

HCID 695487094-[(8-Cyclopropyl-3,4-dihydro-4,4-dimethylspiro[-2H-1-benzopyran-2,1'-cyclopropane]-6-yl)ethynyl]-2-fluoro-benzeneacetic acid methyl ester

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8058HexaneSolvent

Procedure

Following general procedure F and using 8-cyclopropyl-6-ethynyl-3,4-dihydro-4,4-dimethylspiro[2H-1-benzopyran-2,1′-cyclopropane] (Intermediate 44, 0.125 g, 0.5 mmol), methyl-2-fluoro-4-iodo phenyl acetate (Reagent H, 0.14 g, 0.5 mmol), triethyl amine (3 mL), tetrahydrofuran (3 mL), copper(I)iodide (0.020 g, 0.1 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.060 g, 0.085 mmol) followed by preparative normal phase HPLC using 10% ethyl acetate in hexane as the mobile phase, the title compound was obtained (0.096 g, 46%).

Sources & evidence

ORD record
ord-74f72aba7bf246de814005d381b7f9a2
Source dataset
uspto-grants-2002_12
Patent number
US06495552B2

Reaction notes

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