Tert-Butyl nitrite → Methyl 2-[2-(tetrahydropyran-2-yloxy)-phenyl]-3-cyanomethoxy-acrylate

HRID 1600875Notes

Reaction equation

HRID 1600875 reaction equation
N([O:3][C:4]([CH3:7])(C)C)=O.[O:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21](=[CH2:26])[C:22]([O:24][CH3:25])=[O:23].CC(C)([O-])C.[K+].BrCC#[N:36]>C(O)(C)(C)C>[O:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21](=[CH:26][O:3][CH2:4][C:7]#[N:36])[C:22]([O:24][CH3:25])=[O:23]

Participants

6

Reactant 4

HCID 10906Tert-Butyl nitriteHCID 11534BromoacetonitrileHCID 18328184Methyl 2-[2-(tetrahydropyran-2-yloxy)phenyl]-acrylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 54072035Methyl 2-[2-(tetrahydropyran-2-yloxy)-phenyl]-3-cyanomethoxy-acrylateYield 47%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent2×

Procedure

A solution of 34.3 g (300 mmol) of t-butyl nitrite and 25 g (100 mmol) of methyl 2-[2-(tetrahydropyran-2-yloxy)-phenyl]-acrylate in 30 ml of t-butanol is added dropwise to a solution of 12.3 g (110 mmol) of potassium t-butoxide in 120 ml of t-butanol, and the reaction solution warms to 45° C. After 2 hours, 13.2 g (110 mmol) of bromoacetonitrile are added to this mixture and stirring is continued at 20° C. for a further 18 hours. The reaction mixture is concentrated under reduced pressure, taken up in methyl t-butyl ether, washed with water, dried over sodium sulphate and concentrated under reduced pressure. The residue is chromatographed over silica gel using hexane/acetone (8:2). 14.9 g (46.9% of theory) of methyl 2-[2-(tetrahydropyran-2-yloxy)-phenyl]-3-cyanomethoxy-acrylate are obtained.

Workup

  1. customwarms to 45° C
  2. waitis continued at 20° C. for a further 18 hours
  3. concentrationThe reaction mixture is concentrated under reduced pressure
  4. washwashed with water
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is chromatographed over silica gel

Sources & evidence

ORD record
ord-a86f06f4f81f4ff98d74a8bf9ca5ec61
Source dataset
uspto-grants-1999_11
Patent number
US05977123

Reaction notes

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