Tert-butyl 4-isothiocyanatopiperidine-1-carboxylate → tert-Butyl 4-(3-((3SR,5SR)-3-(2-chloro-4-fluorophenyl)-5-hydroxy-2-oxopiperidin-1-yl)thioureido)piperidine-1-carboxylate

HRID 451522Notes

Reaction equation

[NH2:1][N:2]1[CH2:7][CH:6]([OH:8])[CH2:5][CH:4]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=2[Cl:16])[C:3]1=[O:17].[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28]([N:31]=[C:32]=[S:33])[CH2:27][CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]>CC(N(C)C)=O.C(OCC)(=O)C>[Cl:16][C:10]1[CH:11]=[C:12]([F:15])[CH:13]=[CH:14][C:9]=1[CH:4]1[CH2:5][CH:6]([OH:8])[CH2:7][N:2]([NH:1][C:32](=[S:33])[NH:31][CH:28]2[CH2:27][CH2:26][N:25]([C:23]([O:22][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:24])[CH2:30][CH2:29]2)[C:3]1=[O:17]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (3SR,5SR)-1-amino-3-(2-chloro-4-fluorophenyl)-5-hydroxypiperidin-2-one (0.8 g, 2.9 mmol) in dimethylacetamide (1 mL) was added 4-isothiocyanatopiperidine-1-carboxylic acid tert-butyl ester (0.8 g, 3.2 mmol, US2006/14958A1) and the reaction stirred for 2 hours at 80° C. The reaction was diluted with ethyl acetate, washed with water, brine, dried with sodium sulfate and the solvent was evaporated in vacuo. The product was triturated from dichloromethane by addition of heptane to afford the title compound as a colourless powder (1.2 g, 83%). MS ISP (m/e): 501.2 [(M+H)+].

Workup

washwashed with water, brine
dry with materialdried with sodium sulfate
customthe solvent was evaporated in vacuo
customThe product was triturated from dichloromethane by addition of heptane

Sources & evidence

ORD record: ord-7a638818a2e947d88a34a747fd171dd0
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08486967B2

Reaction notes

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