Ethylene Glycol → 1-(Difluoromethyl)-7-[(2,3-difluorophenyl)sulfanyl]-1-methyl-1,2,3,4-tetrahydro[1]benzofuro[2,3-c]pyridine

HRID 1616878Notes

Reaction equation

HRID 1616878 reaction equation
[F:1][CH:2]([F:18])[C:3]1([CH3:17])[C:8]2[O:9][C:10]3[CH:15]=[C:14](I)[CH:13]=[CH:12][C:11]=3[C:7]=2[CH2:6][CH2:5][NH:4]1.[F:19][C:20]1[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=1[S:27][Si](C(C)C)(C(C)C)C(C)C.[F-].[Cs+].C(O)CO.CN(C=O)C>[Cu]I>[F:1][CH:2]([F:18])[C:3]1([CH3:17])[C:8]2[O:9][C:10]3[CH:15]=[C:14]([S:27][C:21]4[CH:22]=[CH:23][CH:24]=[C:25]([F:26])[C:20]=4[F:19])[CH:13]=[CH:12][C:11]=3[C:7]=2[CH2:6][CH2:5][NH:4]1

Participants

7

Reactant 5

HCID 174Ethylene GlycolHCID 6228DimethylformamideHCID 25953Cesium fluorideHCID 67322878(2,3-Difluorophenylsulfanyl)-triisopropylsilaneHCID 673233061-difluoromethyl-7-iodo-1-methyl-1,2,3,4-tetrahydro-benzofuro[2,3-C]pyridine

Product 1

HCID 673234151-(Difluoromethyl)-7-[(2,3-difluorophenyl)sulfanyl]-1-methyl-1,2,3,4-tetrahydro[1]benzofuro[2,3-c]pyridineYield 135.5%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
105 °C

Procedure

Into a Schlenk flask equipped with a magnetic stir bar was added 1-difluoromethyl-7-iodo-1-methyl-1,2,3,4-tetrahydro-benzofuro[2,3-C]pyridine (enantiomer 1, 100 mg, 0.30 mmol), (2,3-difluorophenylsulfanyl)-triisopropylsilane (125 mg, 0.43 mmol), CsF (189 mg, 1.24 mmol), CuI (25 mg, 0.13 mmol), ethylene glycol (85 μL, 1.5 mmol) and anhydrous DMF (3 mL, 0.30 mmol). The Schlenck flask was evacuated and flushed with argon three times. The reaction mixture was heated at 105° C. under argon for 17 h. Upon cooling, the reaction was diluted with DCM, filtered through celite and solvent was evaporated. Purification using preparative TLC (2000 micron silica gfel plate; elution with 15% EtOAc in dichloromethane) afforded 155 mg of product as a viscous, pale oil. MS m/z: 382 [M+H]+.

Workup

  1. customInto a Schlenk flask equipped with a magnetic stir bar
  2. customThe Schlenck flask was evacuated
  3. customflushed with argon three times
  4. temperatureUpon cooling
  5. additionthe reaction was diluted with DCM
  6. filtrationfiltered through celite and solvent
  7. customwas evaporated
  8. customPurification
  9. washTLC (2000 micron silica gfel plate; elution with 15% EtOAc in dichloromethane)

Sources & evidence

ORD record
ord-3380e2749444467abff963aa8ef3d12e
Source dataset
uspto-grants-2014_07
Patent number
US08765779B2

Reaction notes

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