1-Fluoro-3-iodobenzene → 2-{4-[3-(3-Fluorophenyl)prop-2-ynylidene]piperidin-1-yl}-4-methoxynicotinonitrile

HRID 1896032Notes

Reaction equation

HRID 1896032 reaction equation
C[Si](C)(C)C#CC=C1CCNCC1.[CH3:14][O:15][C:16]1[C:21]([C:22]#[N:23])=[C:20]([N:24]2[CH2:29][CH2:28][C:27](=[CH:30][C:31]#[C:32][Si](C)(C)C)[CH2:26][CH2:25]2)[N:19]=[CH:18][CH:17]=1.Br[C:38]1[CH:43]=[C:42]([F:44])[CH:41]=[C:40](F)[CH:39]=1.IC1C=C(F)C=CC=1.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>>[F:44][C:42]1[CH:41]=[C:40]([C:32]#[C:31][CH:30]=[C:27]2[CH2:28][CH2:29][N:24]([C:20]3[N:19]=[CH:18][CH:17]=[C:16]([O:15][CH3:14])[C:21]=3[C:22]#[N:23])[CH2:25][CH2:26]2)[CH:39]=[CH:38][CH:43]=1

Participants

6

Reactant 5

HCID 707251-Fluoro-3-iodobenzeneHCID 1363131-Bromo-3,5-difluorobenzeneHCID 162116731-Butanaminium, N,N,N-tributyl-, fluoride, hydrateHCID 575749824-(3-Trimethylsilylprop-2-ynylidene)piperidineHCID 866273514-Methoxy-2-(4-(3-(trimethylsilyl)prop-2-ynylidene)piperidin-1-yl)nicotinonitrile

Product 1

HCID 251817822-{4-[3-(3-Fluorophenyl)prop-2-ynylidene]piperidin-1-yl}-4-methoxynicotinonitrileYield 20.4%

Procedure

The title compound was prepared in the same way as the Compound of Example 274 but replacing Compound 274c with Compound 294a and 1-bromo-3,5-difluorobenzene with 3-iodofluorobenzene and adding 1 molar equivalent of tetrabutylammonium fluoride monohydrate to the starting reaction mixture. Purification by automated flash chromatography (Horizon™-Biotage) PE-EtOAc 100:30, then by CHCl3 followed by a final purification by preparative RP LC-MS chromatography, using MS-C18 XTerra column 30×50 mm eluting with ammonium bicarbonate 20 mM pH 8 buffer-acetonitrile gradient afforded a colourless oil. Yield: 20.4%. LCPREP. Colourless oil. Yield: 20.4%

Workup

  1. customto the starting reaction mixture
  2. customPurification by automated flash chromatography (Horizon™-Biotage) PE-EtOAc 100:30
  3. custompurification by preparative RP LC-MS chromatography
  4. washeluting with ammonium bicarbonate 20 mM pH 8 buffer-acetonitrile gradient
  5. customafforded a colourless oil

Sources & evidence

ORD record
ord-5cbfa89bb20942aea473d80e46a459a6
Source dataset
uspto-grants-2013_08
Patent number
US08518916B2

Reaction notes

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