Tetramethyltin → 3-(4-Fluoro-phenyl)-4-hydroxy-7-methyl-isothiazolo[5,4-c]pyridine-5-carboxylic acid ethyl ester

HRID 1847234Notes

Reaction equation

HRID 1847234 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:23])=[C:8]2[C:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[N:14][S:13][C:9]2=[C:10](I)[N:11]=1)=[O:5])[CH3:2].[CH:24]1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Sn](C)(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Cu]I.CN1C(=O)CCC1>[CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:23])=[C:8]2[C:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[N:14][S:13][C:9]2=[C:10]([CH3:24])[N:11]=1)=[O:5])[CH3:2]

Participants

7

Reactant 3

HCID 11661TetramethyltinHCID 11776TriphenylphosphineHCID 1364135753-(4-Fluoro-phenyl)-4-hydroxy-7-iodo-isothiazolo[5,4-c]pyridine-5-carboxylic acid ethyl ester

Product 1

HCID 1364135763-(4-Fluoro-phenyl)-4-hydroxy-7-methyl-isothiazolo[5,4-c]pyridine-5-carboxylic acid ethyl esterYield 533.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3-(4-fluoro-phenyl)-4-hydroxy-7-iodo-isothiazolo[5,4-c]pyridine-5-carboxylic acid ethyl ester (295 mg, 0.66 mmol), Pd2(dba)3 (60.8 mg, 0.066 mmol), PPh3 (17.4 mg, 0.066 mmol), and NMP (3.3 mL) was stirred at 70° C. for 10 min. After cooling to r. t. CuI (12.6 mg, 0.066 mmol) was added and the reaction mixture was stirred at 70° C. for another 10 min. After cooling to r. t. Me4Sn (0.37 mL, 2.65 mmol) was added and the mixture was stirred at 70° C. for 15 h. After cooling to r. t. the mixture was partitioned between 1 M HCl (28 mL) and EtOAc (60 mL). The organic layer was washed with brine, water, dried over MgSO4, and was then concentrated in vacuo. The residue was purified by flash column chromatography on silica gel. Elution with 0-20% EtOAc/CH2Cl2, gave the title compound as a white solid (117 mg): MS (m/z) 333.2 (M+1).

Workup

  1. temperatureAfter cooling
  2. stirringthe reaction mixture was stirred at 70° C. for another 10 min
  3. temperatureAfter cooling
  4. stirringthe mixture was stirred at 70° C. for 15 h
  5. temperatureAfter cooling
  6. customthe mixture was partitioned between 1 M HCl (28 mL) and EtOAc (60 mL)
  7. washThe organic layer was washed with brine, water
  8. dry with materialdried over MgSO4
  9. concentrationwas then concentrated in vacuo
  10. customThe residue was purified by flash column chromatography on silica gel
  11. washElution with 0-20% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-c6c45df07d15466d97fcb02dce6b822b
Source dataset
uspto-grants-2015_02
Patent number
US08952160B2

Reaction notes

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