Ethynylcyclobutane → HCID 57908178, compound

HRID 513083Notes

Reaction equation

HRID 513083 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[C:4](I)[CH:3]=1.[C:17]([CH:19]1[CH2:22][CH2:21][CH2:20]1)#[CH:18]>CCN(CC)CC.C1COCC1.O.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>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[C:4]([C:18]#[C:17][CH:19]2[CH2:22][CH2:21][CH2:20]2)[CH:3]=1

Participants

8

Reactant 2

HCID 142749EthynylcyclobutaneHCID 53415320tert-Butyl (6-chloro-4-iodopyridin-3-yl)carbamate

Product 1

HCID 57908178HCID 57908178, compoundYield 60%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
25 °C

Procedure

To the solution of tert-butyl 6-chloro-4-iodopyridin-3-ylcarbamate (7.0 g, 19.8 mmol) in Et3N (100 mL) was added the solution of ethynylcyclobutane in THF (prepared in step a), Pd(PPh3)2Cl2 (1.8 g, 2.1 mmol) and CuI (400 mg, 2.1 mmol). The reaction mixture was stirred at 25° C. for 16 h. The mixture was diluted with water and extracted with dichloromethane (3×100 mL). The extract was washed with brine, dried, concentrated in vacuo and purified by chromatography on silica gel (5-10% ethyl acetate in petroleum ether as eluant) to afford tert-butyl 6-chloro-4-(cyclobutylethynyl)pyridin-3-ylcarbamate (3.6 g, 60% yield). 1H NMR (300 MHz, CDCl3) δ: 9.11 (br, s, 1H), 7.22 (s 1H), 6.97 (s, 1H), 3.39-3.25 (m, 1H), 2.48-1.98 (m, 6H), 1.52 (s, 9H).

Workup

  1. extractionextracted with dichloromethane (3×100 mL)
  2. washThe extract was washed with brine
  3. customdried
  4. concentrationconcentrated in vacuo
  5. custompurified by chromatography on silica gel (5-10% ethyl acetate in petroleum ether as eluant)

Sources & evidence

ORD record
ord-a23c33ff524b4689a4c4dc0b9307cf22
Source dataset
uspto-grants-2015_08
Patent number
US09102672B2

Reaction notes

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