Diphosgene → (2S,5R)-tert-butyl 5-(benzyloxy(chlorocarbonyl)amino)-2-(1,2,4-thiadiazol-5-yl)piperidine-1-carboxylate

HRID 515647Notes

Reaction equation

O=C(Cl)[O:3][C:4](Cl)(Cl)[Cl:5].[CH2:9]([O:16][NH:17][C@H:18]1[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@H:21]([C:31]2[S:35][N:34]=[CH:33][N:32]=2)[CH2:20][CH2:19]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C(Cl)Cl>[CH2:9]([O:16][N:17]([C:4]([Cl:5])=[O:3])[C@H:18]1[CH2:23][N:22]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C@H:21]([C:31]2[S:35][N:34]=[CH:33][N:32]=2)[CH2:20][CH2:19]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Diphosgene (360 mg, 1.8 mmol) was added to a solution of (2S,5R)-tert-butyl 5-(benzyloxyamino)-2-(1,2,4-thiadiazol-5-yl)piperidine-1-carboxylate (468 mg, 1.2 mmol) in dry DCM (20 mL) at 0° C. followed by addition of TEA (360 mg, 3.6 mmol). The mixture was stirred at 0° C. for 2 hrs and then quenched with saturated NaHCO3 (20 mL). The reaction mixture was then extracted with DCM (3×) and the combined organic layer was dried over Na2SO4 and concentrated to afford (2S,5R)-tert-butyl 5-(benzyloxy(chlorocarbonyl)amino)-2-(1,2,4-thiadiazol-5-yl)piperidine-1-carboxylate, which was directly used in the next step. ESI-MS (EI+, m/z): 445 [M+H]+.

Workup

customquenched with saturated NaHCO3 (20 mL)
extractionThe reaction mixture was then extracted with DCM (3×)
dry with materialthe combined organic layer was dried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-564b31d00ada4193ae643ee871e21529
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108966B2

Reaction notes

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