tert-Butanol → Benzo[b]thiophene-7-acetonitrile

HRID 1725378Notes

Reaction equation

HRID 1725378 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[C:9]([CH:10]=O)[C:2]1=2.O1CCCC1.[C-]#N.[Li+].[C:20](P(=O)(OCC)OCC)#[N:21].CC(O)(C)C.[I-].[Sm+2].[I-]>O1CCCC1>[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[C:9]([CH2:10][C:20]#[N:21])[C:2]1=2

Participants

7

Reactant 5

HCID 6386tert-ButanolHCID 76257Diethyl cyanophosphonateHCID 107021381-Benzothiophene-7-carbaldehydeHCID 86597616Lithium cyanide tetrahydrofuranHCID 178506586HCID 178506586, compound2×

Product 1

HCID 11446611Benzo[b]thiophene-7-acetonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Add Benzo[b]thiophene-7carboxaldehyde (2.34 g, 14.4 mmol) and lithium cyanide tetrahydrofuran complex (LiCN*1.5 Tetrahydrofuran, 204 mg, 1.44 mmol) to tetrahydrofuran (40 mL) under nitrogen. Add dropwise neat diethyl cyanophosphonate (2.8 mL, 18.4 mmol) to the stirring reaction mixture. Stir at room temp under nitrogen for 60 hours. Add 2-methyl-2-propanol (1.4 mL, 14.6 mmol). Add the reaction mixture via cannula to a stirred 0.1 molar solution of samarium(II) iodide in tetrahydrofuran (360 mL, 36.0 mmol) at 25° C. under nitrogen. If the resulting reaction mixture is not deep blue add al samarium(II) iodide solution until deep blue color persists. Stir the reaction at 25° C. for 1 hour. Concentrate under reduced pressure, dilute with ethyl acetate, diethyl ether (1:1), wash with aqueous 0.1 M hydrochloric acid, and aqueous saturated sodium chloride. Dry the organic phase over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure. Chromatograph on flash silica using a gradient from neat hexane to 25% ethyl acetate in hexane to obtain the title compound as an off-white solid.

Workup

  1. customto the stirring reaction mixture
  2. customIf the resulting reaction mixture
  3. stirringStir
  4. customthe reaction at 25° C. for 1 hour
  5. concentrationConcentrate under reduced pressure
  6. additiondilute with ethyl acetate, diethyl ether (1:1)
  7. washwash with aqueous 0.1 M hydrochloric acid, and aqueous saturated sodium chloride
  8. dry with materialDry the organic phase over anhydrous magnesium sulfate
  9. filtrationfilter
  10. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-d88d40c413e445fbba9aa3e8ccdef938
Source dataset
uspto-grants-2009_02
Patent number
US07491716B2

Reaction notes

Loading…