3-Chlorothiophenol → 6-(3-chlorophenylsulfanyl)-3,4,4a,9a-tetrahydro-1H-benzo[4,5]furo[2,3-c]pyridine-2-carboxylic acid tert-butyl ester

HRID 1616876Notes

Reaction equation

HRID 1616876 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]2[C:14]3[CH:20]=[C:19](I)[CH:18]=[CH:17][C:15]=3[O:16][CH:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[Na+].CC1C=CC2C=CC3C=CC(C)=NC=3C=2N=1.[Cl:44][C:45]1[CH:46]=[C:47]([SH:51])[CH:48]=[CH:49][CH:50]=1>[Cu]I.CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]2[C:14]3[CH:20]=[C:19]([S:51][C:47]4[CH:48]=[CH:49][CH:50]=[C:45]([Cl:44])[CH:46]=4)[CH:18]=[CH:17][C:15]=3[O:16][CH:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 162573-ChlorothiophenolHCID 652372,9-Dimethyl-1,10-phenanthrolineHCID 23676156Sodium t-butoxideHCID 67379552Tert-butyl 6-iodo-3,4,4a,9a-tetrahydro[1]benzofuro[2,3-c]pyridine-2(1H)-carboxylate

Product 1

HCID 673241216-(3-chlorophenylsulfanyl)-3,4,4a,9a-tetrahydro-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 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

Anhydrous DMF was sparged with argon gas for 1 h before being used. 6-Iodo-3,4,4a,9a-tetrahydro-1H-benzofuro[2,3-c]pyridine-2-carboxylic acid tert-butyl ester (80.25 mg, 0.200 mmol) was dissolved into anhydrous DMF (2.50 mL) in a one dram vial. The sodium tert-butoxide (58 mg, 0.60 mmol), neocuproine (4.2 mg, 0.020 mmol) and copper (I) iodide (11 mg, 0.060 mmol) were added sequentially at room temperature. 3-Chlorobenzenethiol (63.6 mg, 0.440 mmol) was added neat last. The reaction was shaken at 110° C. overnight. It was cooled to room temperature and concentrated. The residue was partially dissolved into a 2% MeOH in DCM solvent mixture (2.0 mL) with sonication. Silica gel (˜55 mg) was added into a filter plate. The suspension of product was flushed through the dry silica gel using 2% MeOH in DCM. The eluent was then concentrated to yield crude 6-(3-chlorophenylsulfanyl)-3,4,4a,9a-tetrahydro-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. MS m/z 418 [M+H]+

Workup

  1. customAnhydrous DMF was sparged with argon gas for 1 h
  2. temperatureIt was cooled to room temperature
  3. concentrationconcentrated
  4. dissolutionThe residue was partially dissolved into a 2% MeOH in DCM solvent mixture (2.0 mL) with sonication
  5. additionSilica gel (˜55 mg) was added into a filter plate
  6. additionThe suspension of product
  7. customwas flushed through the dry silica gel using 2% MeOH in DCM
  8. concentrationThe eluent was then concentrated

Sources & evidence

ORD record
ord-3b0f5701782e4ec5b77b16d64567a7b8
Source dataset
uspto-grants-2014_07
Patent number
US08765779B2

Reaction notes

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