Hydrochloric Acid → 1,1-Dimethylethyl 4-cyano-4-(dimethylamino)-1-piperidinecarboxylate

HRID 1500325Notes

Reaction equation

[CH3:1][NH:2][CH3:3].Cl.[CH3:5][NH:6]C.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][C:18](=O)[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9].Cl.[C-]#N.[K+]>CO.O.CCOC(C)=O.CCCCCC>[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][C:18]([C:5]#[N:6])([N:2]([CH3:3])[CH3:1])[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9]

Participants

Conditions

Temperature: 5 °C

Procedure

500 ml (10 eq) dimethylamine solution and 109.9 g (5 eq) dimethylamine hydrochloride were added to a solution of 50 g (1 eq) tert-butyloxycarbonyl-4-oxopiperidine in 100 ml methanol and the mixture was cooled to 5° C. 5 ml (0.1 eq) hydrochloric acid were then added dropwise to the reaction mixture over a period of 10 min and the mixture was stirred for 60 min at room temperature. 48.9 g (3 eq) potassium cyanide were added in portions to this reaction mixture and the mixture was stirred for 24 h at room temperature. The reaction course was monitored by thin-layer chromatography (50% EtOAc/hexane). Once the conversion was complete, 150 ml water were added to the reaction mixture and it was extracted 3 times with 100 ml ethyl acetate. The combined organic phases were dried with Na2SO4. Following removal of the solvent under reduced pressure, crude product was obtained which was recrystallised out of hexane. 57 g (90%) of product were obtained in the form of a colourless solid.

Workup

stirringthe mixture was stirred for 24 h at room temperature
extractionwas extracted 3 times with 100 ml ethyl acetate
dry with materialThe combined organic phases were dried with Na2SO4
customremoval of the solvent under reduced pressure
customcrude product was obtained which
customwas recrystallised out of hexane

Sources & evidence

ORD record: ord-db318b44ff2a4f8db3b088266d8ae392
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206156B2

Reaction notes

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