Triethylamine → HCID 86731570, compound

HRID 1430583Notes

Reaction equation

HRID 1430583 reaction equation
[C:1]([C@H:3]1[CH2:8][N:7]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[C@H:6]([CH3:18])[CH2:5][CH2:4]1)#[CH:2].Br[C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][N:21]=1.C(N(CC)CC)C>CCOC(C)=O.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:26][C:23]1[CH:24]=[CH:25][C:20]([C:2]#[C:1][C@@H:3]2[CH2:4][CH2:5][C@@H:6]([CH3:18])[N:7]([CH2:9][C:10]3[CH:11]=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=3)[CH2:8]2)=[N:21][CH:22]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 27831712-Bromo-5-fluoropyridineHCID 86731568HCID 86731568, compound

Product 1

HCID 86731570HCID 86731570, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A solution of (2R,55)-5-ethynyl-1-(4-methoxybenzyl)-2-methylpiperidine (284 mg, 1.17 mmol), 2-bromo-5-fluoropyridine (226 mg, 1.28 mmol), copper (I) iodide (67 mg, 0.35 mmol), and triethylamine (2.12 mL, 15.2 mmol) was purged subsurface with nitrogen. Palladium tetrakis (135 mg, 0.117 mmol) was added and the reaction was capped and heated at 90° C. overnight. The reaction was diluted with EtOAc and washed with water and then brine. The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude material was purified by silica gel flash chromatography eluting with 0-85% EtOAc in hexanes to provide 5-fluoro-2-{[(3S,6R)-1-(4-methoxybenzyl)-6-methylpiperidin-3-yl]ethynyl}pyridine as a yellow oil, which gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 339.2 for M+H+.

Workup

  1. customthe reaction was capped
  2. washwashed with water
  3. dry with materialThe organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by silica gel flash chromatography
  7. washeluting with 0-85% EtOAc in hexanes

Sources & evidence

ORD record
ord-5e5ec1f01d3c4c44b93c95f5e7f3b072
Source dataset
uspto-grants-2015_01
Patent number
US08940898B2

Reaction notes

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