Triethylamine → 3-(1-Boc-2-(r)-pyrrolidinylmethoxy)-5-(1-octynyl)pyridine

HRID 2305149Notes

Reaction equation

HRID 2305149 reaction equation
[C:1]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19](Br)[CH:20]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH:22]#[C:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29].CCN(CC)CC>C(Cl)Cl.[Cu]I>[C:1]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[CH2:13][O:14][C:15]1[CH:16]=[N:17][CH:18]=[C:19]([C:22]#[C:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[CH:20]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 123701-OctyneHCID 154802363-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridine

Product 1

HCID 229618113-(1-Boc-2-(r)-pyrrolidinylmethoxy)-5-(1-octynyl)pyridineYield 93%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 3-(1-BOC-2-(R)-pyrrolidinylmethoxy)-5-bromopyridine (300 mg, 0.84 mmol), 1-octyne (0.2 mL, 1.4 mmol), Pd(PPh)3Cl2 (12 mg), CuI (catalytic amount) and NEt3 (2.45 mL) in CH2Cl2 (7 mL) was heated at reflux for 16 h. The solvent was removed, and the residue was washed with 10% NaOH then extracted with CH2Cl2. The organic extract was dried (MgSO4) and concentrated. The residue was chromatographed (silica gel; CHCl3/MeOH, 10:1) to afford the title compound (302 mg) that contaminated with starting material.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 16 h
  3. customThe solvent was removed
  4. washthe residue was washed with 10% NaOH
  5. extractionthen extracted with CH2Cl2
  6. extractionThe organic extract
  7. dry with materialwas dried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was chromatographed (silica gel; CHCl3/MeOH, 10:1)

Sources & evidence

ORD record
ord-7477374a8eff4573ba8db11527a307b1
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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