Methyl iodide → tert-Butyl 3-cyano-3-methylazetidine-1-carboxylate

HRID 474002Notes

Reaction equation

HRID 474002 reaction equation
[C:1]([CH:3]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1)#[N:2].[Li+].[CH3:15][Si]([N-][Si](C)(C)C)(C)C.CI>C1COCC1>[C:1]([C:3]1([CH3:15])[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1)#[N:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 106312831-Boc-3-cyanoazetidine

Product 1

HCID 56971684tert-Butyl 3-cyano-3-methylazetidine-1-carboxylateYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of tert-butyl 3-cyanoazetidine-1-carboxylate (0.55 g, 3.04 mmol) in THF (10 ml) was cooled to −78° C. under a nitrogen atmosphere. LHMDS (3.34 ml, 1M THF) was added dropwise and the solution stirred at −78° C. for 1 hr. Methyl iodide was added dropwise and stirring continued for a further 2 h. The reaction was quenched with water and diluted with ethyl acetate. The organic layer was washed with brine, dried (Na2SO4) and concentrated. The residue was purified on silica gel eluting with 20% ethyl acetate/petrol provide the title compound as a pale yellow oil (0.46 g, 77%). 1H NMR (CDCl3) 1.48 (9H, s), 1.71 (3H, s), 3.82 (2H, d), 4.31 (2H, d).

Workup

  1. stirringstirring
  2. waitcontinued for a further 2 h
  3. customThe reaction was quenched with water
  4. additiondiluted with ethyl acetate
  5. washThe organic layer was washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe residue was purified on silica gel eluting with 20% ethyl acetate/petrol

Sources & evidence

ORD record
ord-9683ff5d8006405686e3174971ad912d
Source dataset
uspto-grants-2014_01
Patent number
US08637511B2

Reaction notes

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