Triethylamine → HCID 18396229, compound

HRID 611559Notes

Reaction equation

HRID 611559 reaction equation
I[C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[OH:9].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.Cl.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:3]2[C:2](=[N:7][C:6]([CH3:8])=[CH:5][CH:4]=2)[CH:30]=1)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 899572-Iodo-6-methylpyridin-3-olHCID 11030701(S)-N-Boc-2-ethynylpyrrolidine

Product 1

HCID 18396229HCID 18396229, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolvent2×

Procedure

A 3.10 g (13.2 mmol) sample of 6-iodo-2-picoline-5-ol (Aldrich Chem. Co.) was dissolved in 5 mL of DMF, and (Ph3P)2PdCl2 (0.38 g, 0.50 mmol), CuI (0.377 g, 1.98 mmol) and triethylamine (1.80 mL, 13.2 mmol) were added. The mixture was stirred under N2 at room temperature for 1 hour, then 2.15 g (11 mmol) of 1-BOC-2-(S)-ethynylpyrrolidine, from Example 1c above, dissolved in 1 mL of DMF, was added carefully. The reaction was stirred at 60° C. for 16 hours, then cooled to room temperature. The reaction mixture was diluted with 2 N HCl and extracted with ether. The aqueous layer was adjusted to pH 10 with K2CO3, then extracted with CH2Cl2. The extract was washed with 20% NaOH, brine, dried over MgSO4, and the solvent was removed. The residue was repeatedly dissolved in toluene and distilled to azeotropically remove the DMF. The residue was chromatographed on silica gel, eluting with 100:0 to 50:50 hexane:EtOAc to give 521 mg of title compound: 1H NMR (CDCl3, 300 MHz) δ 1.33 and 1.47 (2 s, 9H), 1.90-2.30 (m, 4H), 2.63 (s, 3H), 3.45-3.65 (m, 2H), 4.95 and 5.10 (2 s, 1H), 5.58 (s, 1H), 7.02 (d, 1H), 7.55 (d, 1H); MS m/z: 303 (M+H)+.

Workup

  1. additionwas added carefully
  2. stirringThe reaction was stirred at 60° C. for 16 hours
  3. temperaturecooled to room temperature
  4. extractionextracted with ether
  5. extractionextracted with CH2Cl2
  6. washThe extract was washed with 20% NaOH, brine
  7. dry with materialdried over MgSO4
  8. customthe solvent was removed
  9. dissolutionThe residue was repeatedly dissolved in toluene
  10. distillationdistilled
  11. customto azeotropically remove the DMF
  12. customThe residue was chromatographed on silica gel
  13. washeluting with 100:0 to 50:50 hexane

Sources & evidence

ORD record
ord-7830641b3ee94d4bbe0a1bcfe086e0ee
Source dataset
uspto-grants-1999_12
Patent number
US06001849

Reaction notes

Loading…