2-Chloro-3-fluoropyridine → Tert-butyl 3-cyano-3-(3-fluoropyridin-2-yl)azetidine-1-carboxylate

HRID 1441239Notes

Reaction equation

HRID 1441239 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].Cl[C:15]1[C:20]([F:21])=[CH:19][CH:18]=[CH:17][N:16]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1(C)C=CC=CC=1.[Cl-].[Na+].O>[C:1]([C:3]1([C:15]2[C:20]([F:21])=[CH:19][CH:18]=[CH:17][N:16]=2)[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1)#[N:2]

Participants

6

Reactant 3

HCID 27827912-Chloro-3-fluoropyridineHCID 3251421Potassium bis(trimethylsilyl)amideHCID 106312831-Boc-3-cyanoazetidine

Product 1

HCID 57425766Tert-butyl 3-cyano-3-(3-fluoropyridin-2-yl)azetidine-1-carboxylateYield 35.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred suspension of tert-butyl 3-cyanoazetidine-1-carboxylate (5 g; 27.43 mmol) and 2-chloro-3-fluoropyridine (5.05 g; 38.41 mmol) in toluene (100 ml) cooled in an acetone/ice bath under an atmosphere of N2, was added a solution of potassium bis(trimethylsilyl)amide (0.5M solution in toluene; 71.34 ml; 35.67 mmol) over 30 minutes keeping the internal temperature below −10° C. The reaction mixture was allowed to warm to ambient temperature, then stirred an additional 2 hours. The reaction was poured into brine (150 ml) and extracted with EtOAc (3×100 ml). The combined organic phase was washed with brine (100 ml), dried (MgSO4), filtered and evaporated to give a brown oil. The crude product was chromatographed on silica gel eluted with 5% EtOAc in DCM to give the desired product as colourless oil (2.67 g).

Workup

  1. temperaturecooled in an acetone/ice bath under an atmosphere of N2
  2. customthe internal temperature below −10° C
  3. extractionextracted with EtOAc (3×100 ml)
  4. washThe combined organic phase was washed with brine (100 ml)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customto give a brown oil
  9. customThe crude product was chromatographed on silica gel
  10. washeluted with 5% EtOAc in DCM

Sources & evidence

ORD record
ord-74a4f507a5f549acaadaa2f11199cac1
Source dataset
uspto-grants-2010_02
Patent number
US07655644B2

Reaction notes

Loading…