Acetic Acid → 1-Benzhydryl-3-ethylaminoazetidine-3-carbonitrile

HRID 1246796Notes

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.[CH2:20]([NH2:22])[CH3:21].C(O)(=O)C.[C-:27]#[N:28].[K+]>CO>[CH:1]([N:14]1[CH2:17][C:16]([NH:22][CH2:20][CH3:21])([C:27]#[N:28])[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

Conditions

Temperature: 60 °C

Procedure

To a mixture of 1-benzhydrylazetidin-3-one (9.5 g, 40 mmol) in methanol (30 ml) was added ethylamine hydrochloride (4.2 g, 52 mmol) and then acetic acid (3.0 ml, 52 mmol) at room temperature. After stirring for 15 minutes, solid KCN (3.4 g, 52 mmol) was added and the homogeneous mixture was heated at 60° C., overnight. The reaction was cooled and then concentrated, in vacuo. The residue was then extracted from saturated aqueous sodium bicarbonate with ethyl acetate, the combined organic layers were washed with brine, dried (MgSO4), and then concentrated, in vacuo, to afford I-(13A-9)d as a colorless solid (11.7 g, quantitative): +ES MS (M+1) 292.2; 1H NMR (400 MHz, CD3OD) δ 7.42 (d, J=7.5 Hz, 4H), 7.26 (t, J=7.5 Hz, 4H), 7.17 (t, J=7.3 Hz, 2H), 4.47 (s, 1H), 3.54 (d, J=8.3 Hz, 2H), 3.25 (d, J=8.3 Hz, 2H), 2.61 (s, J=7.2 Hz, 2H), 1.11 (t, J=7.3 Hz, 3H).

Workup

customat room temperature
temperatureThe reaction was cooled
concentrationconcentrated, in vacuo
extractionThe residue was then extracted from saturated aqueous sodium bicarbonate with ethyl acetate
washthe combined organic layers were washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated, in vacuo
customto afford I-(13A-9)d as a colorless solid (11.7 g, quantitative)

Sources & evidence

ORD record: ord-a207476dfc1c4bd3b1bfd5b71dfcf03a
Source dataset: uspto-grants-2006_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07129239B2

Reaction notes

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