Water → (3R,4S)-4-azido-1-(3-nitro-5-(4H-1,2,4-triazol-4-yl)phenyl)piperidin-3-ol

HRID 889429Notes

Reaction equation

F[C:2]1[CH:3]=[C:4]([N:11]2[CH:15]=[N:14][N:13]=[CH:12]2)[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1.[N:16]([CH:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH:20]1[OH:25])=[N+:17]=[N-:18].C([O-])([O-])=O.[K+].[K+].O>CS(C)=O>[N:16]([C@H:19]1[CH2:24][CH2:23][N:22]([C:2]2[CH:3]=[C:4]([N:11]3[CH:15]=[N:14][N:13]=[CH:12]3)[CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=2)[CH2:21][C@H:20]1[OH:25])=[N+:17]=[N-:18]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-(3-fluoro-5-nitrophenyl)-4H-1,2,4-triazole (200 mg, 0.96 mmol), 4-azidopiperidin-3-ol (164 mg, 1.15 mmol) and K2CO3 (199 mg, 1.44 mmol) in DMSO was heated at 100° C. for 4 hours. The reaction mixture was poured into water and extracted with EtOAc (two times). The combined extracts were washed with water and brine, dried over MgSO4, filtered and concentrated. The crude material was purified by flash chromatography, (SiO2, 24 g column, 0-12% MeOH/DCM) to give Intermediate 33A (135 mg, 43%) as a yellow solid. HPLC: Rt=1.722 min. (CHROMOLITH® column 4.6×50 mm eluting with 10-90% aqueous methanol over 4 min. containing 0.1% TFA, 4 mL/min., monitoring at 220 nm). MS (ES): m/z=331 [M+H]+.

Workup

extractionextracted with EtOAc (two times)
washThe combined extracts were washed with water and brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude material was purified by flash chromatography, (SiO2, 24 g column, 0-12% MeOH/DCM)

Sources & evidence

ORD record: ord-838c8cb8d3aa4c3f8b54f7bcc037daa2
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08252795B2

Reaction notes

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