Triethylamine → HCID 22872639, compound

HRID 365852Notes

Reaction equation

HRID 365852 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:5]=[N:6][C:7]=1[Cl:8].[CH:23]#[C:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30].C(N(CC)CC)C>C(Cl)Cl.[Cu]I>[C:23]([C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@H:11]2[CH2:15][CH2:14][CH2:13][N:12]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:5]=[N:6][C:7]=1[Cl:8])#[C:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 123701-OctyneHCID 22872666HCID 22872666, compound

Product 1

HCID 22872639HCID 22872639, compoundYield 72.3%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-bromo-6-chloro-3-(1-BOC-2-(R)-pyrrolidinylmethoxy)pyridine from Example 69a (425 mg, 1.1 mmol), 1-octyne (0.2 mL, 1.4 mmol), Pd(PPh)3Cl2 (20 mg), CuI (catalytic amount) and triethylamine (0.5 mL) in CH2Cl2 (8 mL) was heated at reflux for 16 hours. Heating was continued until no starting material remained. The solvent was removed, and the residue was washed with 10% NaOH then extracted with CH2Cl2. The organic extract was dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with hexane:Et2O 100:6-100:15 to afford to give the title compound (335 mg, 72% yield). MS (CI/NH3) m/z 421 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ0.90 (m, 3H), 1.32 (m, 4H), 1.48 (s, 9H), 1.49 (m, 2H), 1.62 (m, 2H), 1.88 (m, 2H), 2.00 (m, 2H), 2.48 (m, 2H), 3.34 (m, 2H), 3.90 (m, 1H), 4.12 (m, 2H), 7.30 (br s, 1H), 7.98 (m, 1H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 16 hours
  3. temperatureHeating
  4. customThe solvent was removed
  5. washthe residue was washed with 10% NaOH
  6. extractionthen extracted with CH2Cl2
  7. extractionThe organic extract
  8. dry with materialwas dried over MgSO4
  9. concentrationconcentrated
  10. customThe residue was chromatographed on a silica gel column
  11. washeluting with hexane:Et2O 100:6-100:15
  12. customto afford

Sources & evidence

ORD record
ord-79ff274bcf564caba912abeba9bee981
Source dataset
uspto-grants-2000_10
Patent number
US06127386

Reaction notes

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