4-Toluenesulfonyl chloride → HCID 11164277, compound

HRID 1768003Notes

Reaction equation

HRID 1768003 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]=[C:7]([CH2:10][CH2:11]O)[C:6]=2[CH:13]=1.[C:14]1([CH3:24])[CH:19]=[CH:18][C:17](S(Cl)(=O)=O)=[CH:16][CH:15]=1.S(C1C=CC(C)=CC=1)([O-])(=O)=O.[NH:36]1[CH2:41][CH:40]=[C:39](N2C3C(=CC=CC=3)C=C2)[CH2:38][CH2:37]1.[CH:51]([N:54](CC)C(C)C)(C)C>N1C=CC=CC=1.CS(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]=[C:7]([CH2:10][CH2:11][N:36]3[CH2:37][CH:38]=[C:39]([C:24]4[C:14]5[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=5)[NH:54][CH:51]=4)[CH2:40][CH2:41]3)[C:6]=2[CH:13]=1

Participants

8

Reactant 5

HCID 73974-Toluenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 85570p-ToluenesulfonateHCID 18184294HCID 18184294, compoundHCID 23001082(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole

Product 1

HCID 11164277HCID 11164277, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 1049PyridineSolvent

Procedure

To a stirred solution of 2-(5-fluoro-1-benzofuran-3-yl)ethanol (900 mg, 5 mmol) in anhydrous pyridine (20 ml), p-toluenesulfonyl chloride (1.14 g, 6.0 mmol) was added. The reaction mixture was kept at 0° C. for 48 hrs and quenched with ice cold water. The reaction mixture was extracted with chloroform, washed well with water and dried over anhydrous MgSO4. It was filtered and concentrated. The crude product obtained was taken to next step without any purification. A mixture of tosylate (334 mg. 1 mmol) (obtained by the above mentioned process) and 3 (1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (198 mg, 1 mmol) was heated at 120° C. in DMSO in the presence of N,N-diisopropylethylamine (5 ml, excess) for 24 hrs. At the end, the reaction mixture was quenched with water and extracted with chloroform. The organic layer was washed with water and dried over anhydrous MgSO4 and concentrated to dryness. The dark colored solid was purified by silica-gel column chromatography by eluting it with 70% ethyl acetate:hexane. 3-{1-[2-(5-fluoro-1-benzofuran-3-yl)ethyl]-1,2,3,6-tetrahydro-4-pyridinyl}-1H-indole was isolated as yellow solid. mp 158° C.; Yield: 140 mg (38%); 361 (M+H); 1H NMR: δ 8.2 (bs, 1H), 7.9 (d,1H), 7.59 (s, 1H), 7.45–7.0 (m, 7H), 6.3 9s, 1H), 3.4 (m, 2H), 3.0 (m, 2H), 2.84 (m, 4H), 2.68 (m, 2H).

Workup

  1. customquenched with ice cold water
  2. extractionThe reaction mixture was extracted with chloroform
  3. washwashed well with water
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationIt was filtered
  6. concentrationconcentrated
  7. customThe crude product obtained
  8. customwas taken to next step without any purification
  9. customobtained by the
  10. customAt the end, the reaction mixture was quenched with water
  11. extractionextracted with chloroform
  12. washThe organic layer was washed with water
  13. dry with materialdried over anhydrous MgSO4
  14. concentrationconcentrated to dryness
  15. customThe dark colored solid was purified by silica-gel column chromatography
  16. washby eluting it with 70% ethyl acetate

Sources & evidence

ORD record
ord-fc4e52c52f0549dabf628db1667cf530
Source dataset
uspto-grants-2007_06
Patent number
US07235569B2

Reaction notes

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