tert-Butanol → [5-(Tetrahydropyran-2-yloxy)benzofur-7-yl]acetonitrile

HRID 910087Notes

Reaction equation

HRID 910087 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C:8]1[CH:9]=[C:10]([CH:17]=O)[C:11]2[O:15][CH:14]=[CH:13][C:12]=2[CH:16]=1.[C-]#N.[Li+].O1CCCC1.[C:27](P(=O)(OCC)OCC)#[N:28].C(O)(C)(C)C>O1CCCC1>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][C:8]1[CH:9]=[C:10]([CH2:17][C:27]#[N:28])[C:11]2[O:15][CH:14]=[CH:13][C:12]=2[CH:16]=1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 76257Diethyl cyanophosphonateHCID 179856275-(Tetrahydropyran-2-yloxy)benzofuran-7-carboxaldehydeHCID 86597616Lithium cyanide tetrahydrofuran

Product 1

HCID 17985429[5-(Tetrahydropyran-2-yloxy)benzofur-7-yl]acetonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Combine 5-(tetrahydropyran-2-yloxy)benzofuran-7-carboxaldehyde (3.75 g, 0.015 mol) with lithium cyanide-tetrahydrofuran (1:1.5 complex, 0.215 g, 0.1 equivalent) in tetrahydrofuran (80 mL) under nitrogen. Add diethyl cyanophosphonate (3.0 ml, 1.3 equivalents) and stir at 20° C. for 2 days. Add tert-butanol (1.6 mL, 1.1 equivalents) then SmI2 in tetrahydrofuran (0.1 M solution, approximately 400 mL). Concentrate the solution in vacuo then redissolve in a solution of ethyl acetate:diethyl ether (approximately 3:1, 100 mL). Add saturated aqueous ammonium chloride and stir for 20 min, until the release of hydrogen cyanide is complete. Filter to remove insoluble material, then extract against 1 N hydrochloric acid. Dry over sodium sulfate, then filter and concentrate. Purification by a plug column (4:1 hexanes:ethyl acetate) to provide the title compound as a light yellow oil.

Workup

  1. concentrationConcentrate the solution in vacuo
  2. dissolutionthen redissolve in a solution of ethyl acetate
  3. filtrationFilter
  4. customto remove insoluble material
  5. extractionextract against 1 N hydrochloric acid
  6. dry with materialDry over sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate
  9. customPurification by a plug column (4:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-c0e0d9b791a4452c89f25708731d9db8
Source dataset
uspto-grants-2011_09
Patent number
US08022065B2

Reaction notes

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