tert-Butyl methyl ether → HCID 67443150, compound

HRID 1253584Notes

Reaction equation

HRID 1253584 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[CH:9][S:10][C:3]=12.[Li]CCCC.[CH2:16]([O:18][CH:19]([O:27][CH2:28][CH3:29])[CH2:20][N:21]1[CH:25]=[C:24](I)[N:23]=[CH:22]1)[CH3:17].CC(OC)(C)C>C1COCC1.[Cl-].[Cl-].[Zn+2]>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:24]3[N:23]=[CH:22][N:21]([CH2:20][CH:19]([O:27][CH2:28][CH3:29])[O:18][CH2:16][CH3:17])[CH:25]=3)[S:10][C:3]=12

Participants

7

Reactant 4

HCID 15413tert-Butyl methyl etherHCID 112752517-Chlorothieno[3,2-b]pyridineHCID 67442066HCID 67442066, compoundHCID 178418339Butyllithium

Product 1

HCID 67443150HCID 67443150, compoundYield 9.4%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of 7-chlorothieno[3,2-b]pyridine (9.26 g, 54.6 mmol) in THF (88 mL) at −15° C. was added n-BuLi (21.84 mL, 54.6 mmol). After 30 min, a solution of ZnCl2 0.5M in THF (109 mL, 54.6 mmol) was added at −15° C. and the reaction mixture was warmed to RT over 45 min. A solution of palladium tetrakistriphenylphosphine (0.841 g, 0.73 mmol) and iodide 260 (11.29 g, 36.4 mmol) in THF (33 mL) was added and the mixture was heated to reflux for 3 h then concentrated. The residue was diluted with water and ammonium hydroxide and extracted with DCM. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 80 g cartridge; AcOEt/Hex:0/100 to 100/0 over 20 CV) to produce a material that upon trituration with. MTBE afforded the title compound 261 (1.2 g, 3.41 mmol, 9% yield) as light-brown solid. MS (m/z): 437.45 (M+H).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 3 h
  3. concentrationthen concentrated
  4. additionThe residue was diluted with water and ammonium hydroxide
  5. extractionextracted with DCM
  6. extractionThe organic extract
  7. washwas washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by Biotage (SNAP 80 g cartridge; AcOEt/Hex:0/100 to 100/0 over 20 CV)
  12. customto produce a material that upon trituration with

Sources & evidence

ORD record
ord-aa93dc463a57446293a16be328d42a76
Source dataset
uspto-grants-2013_06
Patent number
US08455484B2

Reaction notes

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