Piperidine → HCID 45096684, compound

HRID 730619Notes

Reaction equation

Cl[C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[C:3]=1[C:4]#[N:5].[NH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.C(N1CCCCC1)=O>CCOC(C)=O>[CH3:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:2]([N:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)[C:3]=1[C:4]#[N:5]

Participants

Conditions

Temperature: 150 °C

Procedure

2-Methyl-6-piperidin-1-ylbenzonitrile (1 b) was prepared according to the method described by Grell, W. J. Med. Chem. 1998, 41, 5219. A mixture of 2-chloro-6-methylbenzonitrile (1a, 8.5 g), piperidine (16.6 mL, 3 eq) and N-formyl piperidine (12.5 mL) was heated in an oil bath at 150° C. under N2. After a period of 4 days, HPLC indicated complete conversion of starting materials to product. The reaction mixture was cooled to RT, dissolved in 100 mL of EtOAc, washed with water, 10% HCl, and NaHCO3 (sat), dried over anhydrous MgSO4 and treated with charcoal. The product was concentrated under vacuum to give the crude product (1 b) as pale yellow oil (12.01 g); C18 reversed phase HPLC indicated 88% homogeneity at 220 nm. This crude product was purified by flash column chromatography (hex-EtOAc, 1:0 to 20:1 to 10:1) to afford 2-methyl-6-piperidin-1-ylbenzonitrile (1 b) as colorless oil which solidifies upon standing (˜80% yield).

Workup

temperatureThe reaction mixture was cooled to RT
washwashed with water, 10% HCl, and NaHCO3 (sat)
dry with materialdried over anhydrous MgSO4
additiontreated with charcoal
concentrationThe product was concentrated under vacuum
customto give the crude product (1 b) as pale yellow oil (12.01 g)

Sources & evidence

ORD record: ord-9739da88ce004196ae0111b315b505b4
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07582766B2

Reaction notes

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