Acetic Acid → Tert-butyl 3-cyano-3-(1-methylpiperidin-2-yl)azetidine-1-carboxylate

HRID 2100310Notes

Reaction equation

HRID 2100310 reaction equation
[C:1]([C:3]1([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1)#[N:2].O(C)S([C:24](F)(F)F)(=O)=O.C(O)(=O)C>ClCCCl.[Pt](=O)=O>[C:1]([C:3]1([CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][N:15]2[CH3:24])[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 176Acetic AcidHCID 9526Methyl triflateHCID 57798310Tert-butyl 3-cyano-3-(pyridin-2-yl)azetidine-1-carboxylate

Product 1

HCID 57798312Tert-butyl 3-cyano-3-(1-methylpiperidin-2-yl)azetidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 111,2-DichloroethaneSolvent

Procedure

tert-butyl 3-cyano-3-pyridin-2-ylazetidine-1-carboxylate (14.2 g, 55 mmol) in 1,2-dichloroethane (120 ml) was cooled in an ice-bath and treated with methyl triflate. The reaction was stirred at room temperature for 1 hour then at reflux overnight (no starting material in the solution). The resulting orange/brown precipitate was filtered off and washed with more 1,2-dichloroethane. The solid was then dissolved in ethanol (150 ml) and acetic acid (1.5 eq, 5.5 ml) was added. Platinum dioxide (1.5 g) was added and the reaction hydrogenated on a parr at 40 psi overnight. Tlc and mass spec showed complete conversion. The reaction was filtered under nitrogen and the filtrate was evaporated to dryness to give tert-Butyl 3-cyano-3-(1-methylpiperidin-2-yl)azetidine-1-carboxylate as an oil which was used without further purification. m/z (M++H) 280.

Workup

  1. temperatureat reflux overnight (no starting material in the solution)
  2. filtrationThe resulting orange/brown precipitate was filtered off
  3. washwashed with more 1,2-dichloroethane
  4. dissolutionThe solid was then dissolved in ethanol (150 ml)
  5. customthe reaction hydrogenated on a parr at 40 psi overnight
  6. filtrationThe reaction was filtered under nitrogen
  7. customthe filtrate was evaporated to dryness

Sources & evidence

ORD record
ord-518aeba603594ec5867c513fea228dec
Source dataset
uspto-grants-2009_08
Patent number
US07572792B2

Reaction notes

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