Pyridine → HCID 68826481, compound

HRID 230751Notes

Reaction equation

HRID 230751 reaction equation
Br[C:2]1[C:3]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:4][C:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[N:6][CH:7]=1.[CH3:20][Si:21]([C:24]#[CH:25])([CH3:23])[CH3:22].N1C=CC=CC=1.ClC(OCC)=O>C(N(CC)CC)C.C1COCC1.C1COCC1.C(Cl)Cl.C(Cl)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>[CH2:18]([O:17][C:15]([C:3]1[C:2]([C:25]#[C:24][Si:21]([CH3:23])([CH3:22])[CH3:20])=[CH:7][N:6]=[C:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH:4]=1)=[O:16])[CH3:19]

Participants

11

Reactant 4

HCID 1049PyridineHCID 10928Ethyl chloroformateHCID 66111TrimethylsilylacetyleneHCID 68827005HCID 68827005, compound

Product 1

HCID 68826481HCID 68826481, compoundYield 78.1%

Reagents, catalysts & solvents 6

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 21919333Tetrahydrofurane dichloromethaneSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of tert-butyl 5-bromo-4-(ethoxycarbonyl)picolinate (483 mg, 1.4 mmol), trimethylsilylacetylene (206 mg, 2.1 mmol), Pd(PPh3)2Cl2 (99 mg, 0.14 mmol) and CuI (45 mg, 0.21 mmol) in triethylamine (3 mL) and THF (2 mL) in a sealed tube was passed through a stream of Ar for 5 min, and then heated at 105° C. for 1 h. The mixture was diluted with THF/CH2Cl2 (1:1), filtered through a pad of Celite®. The filtrate was concentrated in vacuo to give a residue, which was dissolved in CH2Cl2 (5 mL) and pyridine (0.5 mL) at 0° C. To this solution was added ethyl chloroformate (0.25 mL) and the resulting mixture was stirred at 0° C. for 30 min. The mixture was diluted with CH2Cl2, washed with sat. aq. K2HPO4 solution and dried over MgSO4. The product was purified by flash column chromatography (SiO2, 10% EtOAc/CH2Cl2) to afford a yellow solid (380 mg, 75%). LC-MS: m/z 363 (M+H)+.

Workup

  1. filtrationfiltered through a pad of Celite®
  2. concentrationThe filtrate was concentrated in vacuo
  3. customto give a residue, which
  4. customat 0° C
  5. washwashed with sat. aq. K2HPO4 solution
  6. dry with materialdried over MgSO4
  7. customThe product was purified by flash column chromatography (SiO2, 10% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-c315f5398de647d6a399b13db804ae96
Source dataset
uspto-grants-2009_07
Patent number
US07566784B2

Reaction notes

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