2,9-Dimethyl-1,10-phenanthroline → 7-(3,5-difluoro-phenylsulfanyl)-3,4-dihydro-1H-benzo[4,5]furo[2,3-c]pyridine-2-carboxylic acid tert-butyl ester

HRID 1616875Notes

Reaction equation

HRID 1616875 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[C:14]3[CH:20]=[CH:19][C:18](I)=[CH:17][C:15]=3[O:16][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC1C=CC2C=CC3C=CC(C)=NC=3C=2N=1.[F:38][C:39]1[CH:40]=[C:41]([SH:46])[CH:42]=[C:43]([F:45])[CH:44]=1.CC(C)([O-])C.[Na+]>CN(C=O)C.[Cu]I>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[C:14]3[CH:20]=[CH:19][C:18]([S:46][C:41]4[CH:42]=[C:43]([F:45])[CH:44]=[C:39]([F:38])[CH:40]=4)=[CH:17][C:15]=3[O:16][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 652372,9-Dimethyl-1,10-phenanthrolineHCID 27583613,5-DifluorothiophenolHCID 23676156Sodium t-butoxideHCID 67323433Tert-butyl 7-iodo-3,4-dihydro[1]benzofuro[2,3-c]pyridine-2(1H)-carboxylate

Product 1

HCID 673243367-(3,5-difluoro-phenylsulfanyl)-3,4-dihydro-1H-benzo[4,5]furo[2,3-c]pyridine-2-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent4×

Conditions

Temperature
100 °C

Procedure

Anhydrous DMF was sparged with argon gas for 1 h before being used. 560 μL of a 0.625 M stock solution of 7-iodo-3,4-dihydro-1H-benzo[4,5]furo[2,3-c]pyridine-2-carboxylic acid tert-butyl ester P08 (120 mg, 0.300 mmol) in DMF, 300 μL of a 0.10 M stock solution of neocuproine (6.2 mg, 0.030 mmol) in DMF and 580 μL of a 0.310 M stock solution of copper (I) iodide (34 mg, 0.180 mmol) in DMF were added sequentially into a reaction vial. 3,5-Difluorobenzenethiol (96.5 μL, 0.660 mmol, 2.2 eq) was added neat followed by 630 μL of a 1.0 M stock solution of sodium tert-butoxide (60.5 mg, 0.630 mmol) in DMF. The reaction mixture was shaken at 100° C. for 16 h and the solvent was evaporated. The residue was suspended into DCE:MeOH 95:5 (2.0 mL), passed through a silica gel column (1 g) and eluted with DCE:MeOH 95:5 (3×2.0 mL). The eluent was concentrated to yield crude 7-(3,5-difluoro-phenylsulfanyl)-3,4-dihydro-1H-benzo[4,5]furo[2,3-c]pyridine-2-carboxylic acid tert-butyl ester which was used in the next step without further purification.

Workup

  1. customAnhydrous DMF was sparged with argon gas for 1 h
  2. customthe solvent was evaporated
  3. washeluted with DCE:MeOH 95:5 (3×2.0 mL)
  4. concentrationThe eluent was concentrated

Sources & evidence

ORD record
ord-e10a507604bf42ee9522bcbe0ed6b2c6
Source dataset
uspto-grants-2014_07
Patent number
US08765779B2

Reaction notes

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