Water → HCID 66732089, compound

HRID 1963297Notes

Reaction equation

[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][CH:7]2[CH2:12][C:11](=O)[CH2:10][CH2:9][N:8]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:4][CH:3]=1.[N+:23](CS(C1C=CC(C)=CC=1)(=O)=O)#[C-:24].CC(C)([O-])C.[K+].O>COCCOC>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]([CH2:6][CH:7]2[CH2:12][CH:11]([C:24]#[N:23])[CH2:10][CH2:9][N:8]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: -20 °C

Procedure

To a solution of tert-butyl 2-(4-chlorobenzyl)-4-oxopiperidine-1-carboxylate (8.737 g, 26.98 mmol) in DME (200 mL) under nitrogen was added simultaneously 1-(isocyanomethyl-sulfonyl)-4-methylbenzene (7.90 g, 40.47 mmol) in 200 mL DME and potassium tert-butoxide (81 mL, 80.94 mmol) over 1 hour so that the temperature never rose above 0° C. The solution was stirred at −20° C. for 2 h and then let to warm to room temperature overnight. Water (200 mL) was added to the orange reaction mixture and the solution was stirred for 20 min and then extracted with 3× diethyl ether and 3× EtOAc. The organic phases were combined and dried over Na2SO4 and evaporated to give a brown residue. Further purification was done on Biotage (340 g column, 3 runs, heptane/EtOAc, gradient 20-60% EtOAc) to give tert-butyl 2-(4-chlorobenzyl)-4-cyanopiperidine-1-carboxylate (5.54 g, 61%). 1H NMR (400 MHz, cdcl3) δ, 1.21-1.50 (m, 9H), 1.58-2.14 (m, 4H), 2.55-3.27 (m, 4H), 4.06-4.25 (m, 1H), 4.34-4.60 (m, 1H), 7.02-7.34 (m, 4H). MS m/z 235, 237 (M-C5H8O2+H)+

Workup

temperatureto warm to room temperature overnight
stirringthe solution was stirred for 20 min
extractionextracted with 3× diethyl ether and 3× EtOAc
dry with materialdried over Na2SO4
customevaporated
customto give a brown residue
customFurther purification

Sources & evidence

ORD record: ord-06338bfd3aae48369d56df738a3ee2f9
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415378B2

Reaction notes

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