Acetonitrile → 2-[2-[(2R)-2-methylpyrrolidin-1-yl]ethyl]-1-benzofuran-5-carbonitrile

HRID 494846Notes

Reaction equation

[OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1I.[CH2:11]([N:15]1[CH2:19][CH2:18][CH2:17][C@H:16]1[CH3:20])[CH2:12][C:13]#[CH:14].C(#N)C.C(NC(C)C)(C)C>CC([O-])=O.CC([O-])=O.[Pd+2].[Cu](I)I>[CH3:20][C@@H:16]1[CH2:17][CH2:18][CH2:19][N:15]1[CH2:11][CH2:12][C:13]1[O:1][C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=2[CH:14]=1

Participants

Conditions

Temperature: 25 °C

Procedure

The product from Example 87A (10.0 g, 40.81 mmol) was sequentially treated with 0.1M (2R)-1-(3-butynyl)-2-methylpyrrolidine in acetonitrile (490 mL, 48.9 mmol), Pd(OAc)2 (0.275 g, 1.22 mmol), Ptol3 (0.747 g, 2.44 mmol), and copper iodide (1.16 g, 6.122 mmol). After stirring at 25° C. for 10 min, diisopropyl amine (43.0 mL) was added and the reaction mixture was heated at 60° C. in an inert atmosphere for 16 h. The reaction mixture was cooled, filtered through celite, concentrated under reduced pressure, and purified on silica gel using 95% DCM, 9.5% MeOH, 0.1% NH4OH to provide the title compound as a brown semi-solid (2.56 g, 24.6% yield). 1HNMR (300 MHz, CD3OD) δ 1.09 (d, 3H, J=6.1 Hz), 1.46 (m, 1H), 1.81 (m, 2H), 2.02-2.38 (m, 2H), 2.59 (m, 2H) 3.08 (m, 2H), 3.28 (m, 2H), 6.70 (s, 1H), 7.58 (s, 1H), 7.97 (s, 1H); MS (ESI) m/e 255 (M+H)+.

Workup

temperaturethe reaction mixture was heated at 60° C. in an inert atmosphere for 16 h
temperatureThe reaction mixture was cooled
filtrationfiltered through celite
concentrationconcentrated under reduced pressure
custompurified on silica gel using 95% DCM, 9.5% MeOH, 0.1% NH4OH

Sources & evidence

ORD record: ord-51839754a37147709c95513b01ba5b8f
Source dataset: uspto-grants-2009_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07538138B2

Reaction notes

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