Triethylamine → HCID 22872639, compound

HRID 2305147Notes

Reaction equation

HRID 2305147 reaction equation
[C:1]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][O:14][C:15]1[C:16](Cl)=[N:17][C:18]([Cl:21])=[CH:19][CH:20]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH:23]#[C:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30].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][C:18]([Cl:21])=[C:19]([C:23]#[C:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH:20]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 123701-OctyneHCID 22961842HCID 22961842, compound

Product 1

HCID 22872639HCID 22872639, compoundYield 78%

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-(S)-pyrrolidinylmethoxy)-chloro-6-chloropyridine from Example 69a (400 mg, 1.02 mmol), 1-octyne (0.23 mL, 1.54 mmol), Pd(PPh)3Cl2 (36 mg), CuI (catalytic amount) and NEt3 (2.5 mL) in CH2Cl2 (8 mL) was heated at reflux for 16 h. 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 (MgSO4) and concentrated. The residue was chromatographed (silica gel; hexane:EtOAc, 3:1) to afford the title compound (335 mg, 72% yield): 1H NMR (CDCl3, 300 MHz) δ 0.91 (t, J=7.5 Hz, 3H), 1.23-1.40 (m, 4H), 1.48 (s, 9H), 1.56-1.69 (m, 2H), 1.81-2.06 (m, 5H), 2.46 (t, J=7.5 Hz, 2H), 3.27-3.47 (m, 2H), 3.98-4.21 (m, 4H), 7.29 (br, s, 1H), 7.98 (d, J=3.0 Hz, 1H); MS (CI/NH3) m/z 421 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 16 h
  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 (MgSO4)
  9. concentrationconcentrated
  10. customThe residue was chromatographed (silica gel; hexane:EtOAc, 3:1)

Sources & evidence

ORD record
ord-11df248c6c9e4ba68979b68b2b0e59b8
Source dataset
uspto-grants-2002_08
Patent number
US06437138B1

Reaction notes

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