Diisopropylethylamine → tert-butyl (3R,4R,5S)-4-(tert-butyldimethylsilyloxy)-5-methyl-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamate

HRID 924429Notes

Reaction equation

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

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-chloro-3-nitropyridine (96.6 mg, 0.609 mmol), tert-butyl ((3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-3-yl)carbamate (300 mg, 0.609 mmol) and DIPEA (0.319 mL, 1.83 mmol) in isopropyl alcohol (20 mL) was stirred at 100° C. for 4 h. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified by flash chromatography on silica using a CombiFlash® apparatus (eluting with 0 to 30% EtOAc in hexanes) to give the sub-title compound as a pale yellow powder (1.93 g). LCMS calc. for C22H39N4O5Si (M+H)+: m/z=467.3. found: 467.1.

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
customThe resulting residue was purified by flash chromatography on silica using
washa CombiFlash® apparatus (eluting with 0 to 30% EtOAc in hexanes)

Sources & evidence

ORD record: ord-8473d226162a4fe1b6a0be419a6780be
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278950B2

Reaction notes

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