Triethylamine → HCID 18396230, compound

HRID 611588Notes

Reaction equation

HRID 611588 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([OH:9])[C:5](I)=[N:6][CH:7]=1.C(N(CC)CC)C.[C:17]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]#[CH:30])([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]>CN(C=O)C.CCOCC.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:17]([N:24]1[CH2:28][CH2:27][CH2:26][C@H:25]1[C:29]1[O:9][C:4]2[C:5](=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=2)[CH:30]=1)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 11030701(S)-N-Boc-2-ethynylpyrrolidineHCID 226029855-Bromo-2-iodopyridin-3-ol

Product 1

HCID 18396230HCID 18396230, compoundYield 43.6%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

A sample of 5-bromo-2-iodo-3-pyridinol (0.60 g, 2.0 mmol), from above, was dissolved in DMF (3 mL), and Pd(PPh3)2Cl2 (0.07 g, 0.1 mmol), CuI (0.077 g, 0.4 mmol) and triethylamine (0.33 mL, 2.4 mmol) were added. The mixture was stirred under N2 at room temperature for 1 hour, then 1-BOC-2-(S)-ethynylpyrrolidine (0.429 g, 2.2 mmol), from Example 1c above, dissolved in DMF (1 mL), was added carefully. The reaction mixture was stirred at 60° C. for 16 hours, then cooled to room temperature. The reaction mixture was diluted with ether, then washed with 10% NaOH and brine. The organic extract was dried over MgSO4 and concentrated. The residue was chromatographed (silica gel; hexane/EtOAc, 5:1 to 2:1) to give the title compound (0.32 g, 43%): 1H NMR (CDCl3, 300 MHz) δ 1.32, 1.46 (2 s, 9H), 1.91-2.40 (m, 4H), 3.37-3.70 (m, 2H), 4.93-5.15 (m, 1H), 6.66 (s, 1H), 7.85 (s, 1H), 8.55 (s, 1H); MS (CI/NH3) m/z: 367, 369 (M+H)+.

Workup

  1. additionwas added carefully
  2. stirringThe reaction mixture was stirred at 60° C. for 16 hours
  3. temperaturecooled to room temperature
  4. washwashed with 10% NaOH and brine
  5. extractionThe organic extract
  6. dry with materialwas dried over MgSO4
  7. concentrationconcentrated
  8. customThe residue was chromatographed (silica gel; hexane/EtOAc, 5:1 to 2:1)

Sources & evidence

ORD record
ord-4746b11b141741eb92db99928f9ccb5d
Source dataset
uspto-grants-1999_12
Patent number
US06001849

Reaction notes

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