Sodium Hydroxide → 2-Benzo[b]thiophen-5-yl-3-cyclopentyl-propionitrile

HRID 546252Notes

Reaction equation

HRID 546252 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH2:10][C:11]#[N:12])[CH:8]=[CH:9][C:2]1=2.[OH-].[Na+].C(OC(=O)NC1C=CC=C(CN2C=CC(NC(=O)[C@@H](C3C=CC(S(C)(=O)=O)=C(Cl)C=3)[CH2:37][CH:38]3[CH2:42][CH2:41][CH2:40][CH2:39]3)=N2)C=1)(C)(C)C>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O.C(Cl)Cl>[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH:10]([CH2:37][CH:38]3[CH2:42][CH2:41][CH2:40][CH2:39]3)[C:11]#[N:12])[CH:8]=[CH:9][C:2]1=2

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 20509997(Benzo[b]thiophen-5-yl)acetonitrileHCID 67190452HCID 67190452, compound

Product 1

HCID 671896902-Benzo[b]thiophen-5-yl-3-cyclopentyl-propionitrileYield 40.3%

Reagents, catalysts & solvents 3

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

In a round bottom flask was placed benzo[b]thiophen-5-yl-acetonitrile (700 mg, 4.04 mmol), tetrabutyl ammonium hydrogen sulfate (1.37 g, 4.04 mmol) and a 47% by weight solution of aqueous sodium hydroxide (646 μl, 8.08 mmol). To this well stirred mixture was added iodomethylcyclopentane (prepared in PCT WO 2004/052869 A1 Example 1, 1.69 g, 8.08 mmol) and the vigorously stirred mixture was heated to reflux for 6 h. The reaction was then diluted with water (5 mL) and methylene chloride (10 mL) and extracted with methylene chloride (3×20 mL). The organics were combined and dried over sodium sulfate, filtered and concentrated in vacuo. Purification an AnaLogix Intelliflash system (40 g column, 3% ethyl acetate/hexanes to 5% ethyl acetate/hexanes) afforded 2-benzo[b]thiophen-5-yl-3-cyclopentyl-propionitrile (416 mg, 40%) as a yellow oil: ES-HRMS m/e calcd for C16H17NS (M+H)+ 256.115, observed 256.115.

Workup

  1. customIn a round bottom flask was placed
  2. temperaturethe vigorously stirred mixture was heated
  3. temperatureto reflux for 6 h
  4. extractionextracted with methylene chloride (3×20 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customPurification an AnaLogix Intelliflash system (40 g column, 3% ethyl acetate/hexanes to 5% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-cbb51634b540448ea5a4344578a510fa
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

Loading…