Ethyl6-iodonicotinoate → HCID 21846664, compound

HRID 619630Notes

Reaction equation

HRID 619630 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[S:9][C:8]([CH3:14])([CH3:13])[CH2:7][C:6]2=[O:15])#[CH:2].I[C:17]1[CH:27]=[CH:26][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][N:18]=1>CCN(CC)CC.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>[CH3:14][C:8]1([CH3:13])[CH2:7][C:6](=[O:15])[C:5]2[C:10](=[CH:11][CH:12]=[C:3]([C:1]#[C:2][C:17]3[CH:27]=[CH:26][C:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:19][N:18]=3)[CH:4]=2)[S:9]1

Participants

6

Reactant 2

HCID 10891136Ethyl6-iodonicotinoateHCID 21957876HCID 21957876, compound2×

Product 1

HCID 21846664HCID 21846664, compoundYield 78.3%

Reagents, catalysts & solvents 3

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

Procedure

A solution of 6-ethynyl-2,2-dimethylthiochroman-4-one (Compound 222, 510.0 mg, 2.36 mmol) and ethyl 6-iodonicotinate (654.0 mg, 2.36 mmol) in 20.0 mL Et3N was purged with argon for 20 minutes. To this solution was added bis(triphenylphosphine)-palladium(II) chloride (425.0 mg, 0.60 mmol) and copper(I) iodide (115.0 mg, 0.60 mmol). After sparging for an additional 10 minutes with argon, the solution was stirred overnight at room temperature. The reaction mixture was diluted with EtOAc (20 mL) and filtered through a pad of Celite using an Et2O wash. Concentration of the filtrate under reduced pressure, followed by column chromatography (10 to 20% EtOAc/hexanes) of the residual solid afforded 675 mg (78%) of the title compound as an orange solid. 1H NMR (300 MHz, CDCl3) δ: 9.20 (1H, d, J=1.0 Hz), 8.34 (1H, d, J=1.8 Hz), 8.29 (1H, dd, J=2.2, 8.2 Hz), 7.60 (2H, m), 7.25 (1H, d, J=8.4 Hz), 4.43 (2H, q, J=7.1 Hz), 2.90 (2H, s), 1.49 (6H, s), 1.43 (3H, t, J=7.1 Hz).

Workup

  1. customAfter sparging for an additional 10 minutes with argon
  2. additionThe reaction mixture was diluted with EtOAc (20 mL)
  3. filtrationfiltered through a pad of Celite
  4. washwash

Sources & evidence

ORD record
ord-652da260298f4e1ab9b903a31e734d83
Source dataset
uspto-grants-1999_09
Patent number
US05958954

Reaction notes

Loading…