1H-1,2,4-Triazole → 1,1-Dimethylethyl 4-(1H-1,2,4-triazol-1-yl)-1-piperidinecarboxylate

HRID 1987754Notes

Reaction equation

CS(O[CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)(=O)=O.[NH:19]1[CH:23]=[N:22][CH:21]=[N:20]1.[H-].[Na+].S([O-])(=O)(=O)C>CN(C=O)C>[N:19]1([CH:6]2[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]2)[CH:23]=[N:22][CH:21]=[N:20]1

Participants

Conditions

Temperature: 60 °C

Procedure

To a stirred solution of: tert-butyl 4-[(methylsulfonyl)oxy]piperidine-1-carboxylate (5.9 g, 21 mmol) and 1,2,4-triazole (1.8 g, 25 mmol equiv.) in DMF at ambient temperature was added sodium hydride (60% in mineral oil, 1.0 g, 25 mmol). The mixture was stirred at 60° C. for 5 days, and the TLC showed no starting mesylate left. The mixture was poured into ice water and extracted with ethyl acetate (3×). The organic layer was dried, evaporated and purified by silica flash column eluting with 0-10% methanol in ethyl acetate to give tert-butyl 4-(1H-1,2,4-triazol-1-yl)piperidine-1-carboxylate as a white solid. The solid was then treated with hydrogen chloride in dioxane (4 N, 10 mL) for 2 h. The mixture was then evaporated to remove most of the dioxane to give a white solid, which was washed with ethyl acetate to give the desired 4-(1H-1,2,4-triazol-1-yl)piperidine hydrochloride salt (5.55 g). 1H NMR (300 MHz, CD3OD): δ 10.00 (s, 1H), 8.97 (s, 1H), 5.10-5.00 (m, 1H), 3.63-3.58 (br. d, 2H), 3.33-3.26 (br. d, 2H), 2.50-2.30 (m, 4H).

Workup

waitleft
extractionextracted with ethyl acetate (3×)
customThe organic layer was dried
customevaporated
custompurified by silica flash column
washeluting with 0-10% methanol in ethyl acetate

Sources & evidence

ORD record: ord-be914902e67b47e2bd7c12073712c0b4
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07553841B2

Reaction notes

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