2-Chloropyridine → HCID 117702602, compound

HRID 1503257Notes

Reaction equation

HRID 1503257 reaction equation
[C:1]([C:3]12[CH2:10][C:7]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])([CH2:8][CH2:9]1)[CH2:6][CH2:5][CH2:4]2)#[CH:2].Cl[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1>C(#N)C.C(OCC)(=O)C.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.[Cu]I>[N:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:2]#[C:1][C:3]12[CH2:10][C:7]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:17])[CH3:16])([CH2:8][CH2:9]1)[CH2:6][CH2:5][CH2:4]2

Participants

7

Reactant 2

HCID 79772-ChloropyridineHCID 117702551HCID 117702551, compound

Product 1

HCID 117702602HCID 117702602, compoundYield 76.3%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a stirred solution of tert-butyl 5-ethynylbicyclo[3.2.1]octan-1-ylcarbamate (5.8 g, 23.3 mmol) and 2-chloropyridine (3.18 g, 28 mmol) in TEA (30 mL) and acetonitrile (150 mL) under N2 was added Pd(PPh3)4 (266 mg, 0.23 mmol), followed by CuI (266 mg, 1.4 mmol). The reaction mixture was heated at 70° C. for three hours. After cooled to room temperature, the reaction mixture was diluted with ethyl acetate (250 mL), washed with water (150 mL) and brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=5/1) to give 5.8 g (76%) of the title compound, tert-butyl 5-(pyridin-2-ylethynyl)bicyclo[3.2.1]octan-1-ylcarbamate, as a white solid. ESI-MS m/z: 298 (M-55)+.

Workup

  1. temperatureAfter cooled to room temperature
  2. washwashed with water (150 mL) and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=5/1)

Sources & evidence

ORD record
ord-19cf2167111047d69a793474146f8914
Source dataset
uspto-grants-2015_12
Patent number
US09212165B2

Reaction notes

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