Tetrahydrofuran → 1-[5-(4-Fluoro-phenylethynyl)-pyridin-2-yl]-4,4-dimethyl-pyrrolidin-2-one

HRID 629237Notes

Reaction equation

[CH3:1][C:2]1([CH3:20])[CH2:6][N:5]([C:7]2[N:12]=[CH:11][C:10]([C:13]#[C:14][Si](C)(C)C)=[CH:9]N=2)[C:4](=[O:19])[CH2:3]1.[F:21][C:22]1[CH:27]=[CH:26][C:25](I)=[CH:24][CH:23]=1.[CH3:29]CN(CC)CC.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1COCC1>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:14]#[C:13][C:10]2[CH:9]=[CH:29][C:7]([N:5]3[CH2:6][C:2]([CH3:1])([CH3:20])[CH2:3][C:4]3=[O:19])=[N:12][CH:11]=2)=[CH:24][CH:23]=1

Participants

Conditions

Temperature: 70 °C

Procedure

4,4-Dimethyl-1-(5-trimethylsilanylethynyl-pyrimidin-2-yl)-pyrrolidin-2-one (Example 120, step 2) (30 mg, 0.1 mmol) was dissolved in DMF (1 ml). 1-Fluoro-4-iodobenzene (32 mg, 0.14 mmol, 1.4 equiv.), Et3N (43 μl, 0.31 mmol, 3 equiv.), Bis-(triphenylphosphine)-palladium(II)dichloride (4 mg, 5.2 μmol, 0.05 equiv.) and copper(I)iodide (0.6 mg, 3.1 μmol, 0.03 equiv.) were added under nitrogen and the mixture was heated to 70° C. TBAF 1M in THF (115 μl, 0.115 mmol, 1.1 equiv.) was added dropwise in 20 minutes at 70° C. The reaction mixture was stirred for 30 minutes at 70° C. and evaporated with isolute to dryness. The crude product was purified by flash chromatography with a 20 g silica gel column and eluting with heptane:ethyl acetate 100:0->0:100. The desired 1-[5-(4-fluoro-phenylethynyl)-pyridin-2-yl]-4,4-dimethyl-pyrrolidin-2-one (24 mg, 73% yield) was obtained as a white solid, MS: m/e=310.1 (M+H+).

Workup

customevaporated with isolute to dryness
customThe crude product was purified by flash chromatography with a 20 g silica gel column
washeluting with heptane:ethyl acetate 100:0->0:100

Sources & evidence

ORD record: ord-2e38d0f1d6894151ac61140e58996bfb
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315498B2

Reaction notes

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