2-Fluoropyridine → Tert-butyl 3-cyano-3-(pyridin-2-yl)azetidine-1-carboxylate

HRID 2100301Notes

Reaction equation

HRID 2100301 reaction equation
F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[C:8]([CH:10]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11]1)#[N:9].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[NH4+].[Cl-]>C1COCC1>[C:8]([C:10]1([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11]1)#[N:9]

Participants

6

Reactant 4

HCID 97462-FluoropyridineHCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 106312831-Boc-3-cyanoazetidine

Product 1

HCID 57798310Tert-butyl 3-cyano-3-(pyridin-2-yl)azetidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2-fluoropyridine (2.6 mL, 30.2 mmol) and tert-butyl 3-cyanoazetidine-1-carboxylate (I-1, 5.0 g, 27.5 mmol) in THF (200 mL) at room temperature was treated with LHMDS (55 mL of a 1.0 M solution in THF, 55 mmol). After 6 h, the reaction mixture was poured into saturated aqueous NH4Cl (200 mL) and extracted with EtOAc (3×150 mL). The combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure to afford tert-butyl 3-cyano-3-pyridin-2-ylazetidine-1-carboxylate (I-2) as a yellow-brown oil. Analytical LCMS: single peak (214 nm), 3.004 min. This material was used in subsequent reactions without further purification.

Workup

  1. extractionextracted with EtOAc (3×150 mL)
  2. dry with materialThe combined organic extracts were dried (Na2SO4)
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d0a775f1716949088586b957bc56afdc
Source dataset
uspto-grants-2009_08
Patent number
US07572792B2

Reaction notes

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