2-Bromopyridine → 1-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)-4-(pyridin-2-yl)but-3-yn-1-ol

HRID 546374Notes

Reaction equation

HRID 546374 reaction equation
[CH:1]([C@@H:4]1[CH2:9][CH2:8][C@@H:7]([CH3:10])[CH2:6][C@H:5]1[CH:11]([OH:15])[CH2:12][C:13]#[CH:14])([CH3:3])[CH3:2].Br[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C(N(CC)CC)C>[CH:1]([C@@H:4]1[CH2:9][CH2:8][C@@H:7]([CH3:10])[CH2:6][C@H:5]1[CH:11]([OH:15])[CH2:12][C:13]#[C:14][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 79732-BromopyridineHCID 866439371-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)but-3-yn-1-ol

Product 1

HCID 671891181-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)-4-(pyridin-2-yl)but-3-yn-1-olYield 43.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

To a round bottom flask were added 1-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)but-3-yn-1-ol (0.47 g, 2.3 mmol), triethylamine (10 mL), 2-bromopyridine (0.28 mL, 2.7 mmol), bis(triphenylphosphine)palladium(II) dichloride (16 mg, 0.023 mmol) and copper(I) iodide (9 mg, 0.045 mmol). After this mixture was stirred with heating overnight at 60° C., it was allowed to cool to room temperature. The reaction was mixed directly with silica, concentrated and purified by silica chromatography to give the desired coupling product (286 mg).

Workup

  1. temperatureto cool to room temperature
  2. additionThe reaction was mixed directly with silica
  3. concentrationconcentrated
  4. custompurified by silica chromatography

Sources & evidence

ORD record
ord-43f11b5f8d3d4467a492c2351b454c24
Source dataset
uspto-grants-2011_05
Patent number
US07935848B2

Reaction notes

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