Ammonium Chloride → 3-{1-[6-(2,4-Difluorophenyl)pyridin-2-yl]-2-oxobut-3-yn-1-yl}-4-fluorobenzonitrile

HRID 1360682Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([CH:15]([C:24]2[CH:25]=[C:26]([CH:29]=[CH:30][C:31]=2[F:32])[C:27]#[N:28])[C:16](=[O:23])[C:17]#[C:18][Si](C)(C)C)[CH:12]=[CH:11][CH:10]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].[NH4+].[Cl-]>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([CH:15]([C:24]2[CH:25]=[C:26]([CH:29]=[CH:30][C:31]=2[F:32])[C:27]#[N:28])[C:16](=[O:23])[C:17]#[CH:18])[CH:12]=[CH:11][CH:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3-[1-[6-(2,4-difluorophenyl)pyridin-2-yl]-2-oxo-4-(trimethylsilyl)but-3-yn-1-yl]-4-fluorobenzonitrile (from Step D above, 40 g, 89.0 mmol) in THF (750 mL) was added TBAF (133 mL, 133.6 mmol) at 0° C. After stirring at 0° C. for 15 min, the reaction was poured into aqueous NH4Cl, and extracted with EtOAc (2×). The organic layers were combined, washed with H2O, brine, dried over MgSO4. The mixture was concentrated and purified by silica gel chromatography (hexanes/methylene chloride) to give title compound (24 g). 1H NMR (CDCl3) δ: 7.80 (q, 1H), 7.72 (m, 3H), 7.51 (d, 1H), 7.31 (t, 1H), 7.04 (m, 1H), 6.97 (m, 1H), 6.60 (d, 1H), 3.14 (s, 10H).

Workup

extractionextracted with EtOAc (2×)
washwashed with H2O, brine
dry with materialdried over MgSO4
concentrationThe mixture was concentrated
custompurified by silica gel chromatography (hexanes/methylene chloride)

Sources & evidence

ORD record: ord-ec40c0a15ffd4cbdaaeb1948c2cc5f5c
Source dataset: uspto-grants-2011_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07879875B2

Reaction notes

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