Acetic Acid → 1-(Diphenylmethyl)-3-(methylamino)-3-azetidinecarbonitrile

HRID 2054397Notes

Reaction equation

HRID 2054397 reaction equation
[CH:1]([N:14]1[CH2:17][C:16](=O)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH3:20][NH2:21].C(O)(=O)C.[C-:26]#[N:27].[K+]>CO>[CH:1]([N:14]1[CH2:17][C:16]([NH:27][CH3:26])([C:20]#[N:21])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 9032Potassium CyanideHCID 37355581-(Diphenylmethyl)azetidin-3-oneHCID 6364545Methylamine hydrochloride

Product 1

HCID 219057751-(Diphenylmethyl)-3-(methylamino)-3-azetidinecarbonitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1-benzhydrylazetidin-3-one (2.13 g, 8.98 mmol) in methanol (17 ml) was added methylamine hydrochloride (1.21 g, 18.0 mmol) and then acetic acid (1.03 ml, 18.0 mmol) at room temperature. After stirring for 5 minutes, solid KCN (1.17 g, 18.0 mmol) was added and the mixture was heated to 60° C. for 19 hours. The reaction was cooled; the solid product was collected by vacuum filtration, rinsed with methanol, and then dried, in vacuo, to afford I-3A-2a as a colorless solid (2.50 g, quantitative): +ESI MS (M+1) 278.3; 1H NMR (400 MHz, CD2Cl2) δ 7.43 (d, J=7.5 Hz, 4H), 7.29 (t, J=7.5 Hz, 4H), 7.23 (t, J=7.3 Hz, 2H), 4.45 (s, 1H), 3.55 (d, J=7.5 Hz, 2H), 3.15 (d, J=7.1 Hz, 2H), 2.40 (s, 3H).

Workup

  1. customat room temperature
  2. temperatureThe reaction was cooled
  3. filtrationthe solid product was collected by vacuum filtration
  4. washrinsed with methanol
  5. customdried, in vacuo
  6. customto afford I-3A-2a as a colorless solid (2.50 g, quantitative)

Sources & evidence

ORD record
ord-b1442115b9f645cfbf3c0e7fadf0e988
Source dataset
uspto-grants-2008_02
Patent number
US07329658B2

Reaction notes

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