1,5-Dibromopentane → 3-Ethyl-4-(1-piperidinyl)benzonitrile

HRID 423302

Reaction equation

[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[CH2:10][CH3:11].Br[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]Br.C(=O)([O-])[O-].[K+].[K+]>O>[CH2:10]([C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:2]=1[N:1]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)[C:6]#[N:7])[CH3:11]

Participants

Conditions

Temperature: 160 °C

Procedure

4-Amino-3-ethylbenzonitrile (3.0 g, 20.5 mmol), 1,5-dibromopentane (11.1 mL, 82.1 mmol), potassium carbonate (5.67 g, 41.0 mmol) and water (39.6 mL) were all split equally between ten microwave vials and each heated at 160° C. for 1 h. All reaction mixtures were combined and extracted twice with ethyl acetate (40 mL) and the combined organic fractions dried (phase separator) and concentrated in vacuo. Dichloromethane was added and then the mixture filtered before the filtrate was purified by silica chromatography, eluting 2-5% ethyl acetate in hexane to give the title compound as a colourless oil (823 mg, 3.85 mmol). Analysis indicated that the compound contained a small dibromopentane impurity. δH (methanol-d4, 400 MHz) 7.52 (1H, dd), 7.47 (1H, dd), 7.13 (1H, d), 2.89 (4H, dd), 2.71 (2H, q), 1.76-1.71 (4H, m), 1.64-1.56 (2H, m), 1.25 (3H, t). MS (ES): C14H18N2 requires 214; found 215 (MH+).

Workup

customall split equally between ten microwave vials
customAll reaction mixtures
extractionextracted twice with ethyl acetate (40 mL)
customthe combined organic fractions dried (phase separator)
concentrationconcentrated in vacuo
additionDichloromethane was added
filtrationthe mixture filtered before the filtrate
customwas purified by silica chromatography
washeluting 2-5% ethyl acetate in hexane

Sources & evidence

ORD record: ord-4c515ba76d7440ba856a52cfc26d76c0
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08101775B2

Linked notes

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