Triethylamine → tert-Butyl [(3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methyl-1-(3-methyl-5-nitropyridin-4-yl)piperidin-3-yl]carbamate

HRID 924434Notes

Reaction equation

HRID 924434 reaction equation
[Si:1]([O:8][C@@H:9]1[C@@H:14]([CH3:15])[CH2:13][NH:12][CH2:11][C@H:10]1[NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl[C:25]1[C:30]([N+:31]([O-:33])=[O:32])=[CH:29][N:28]=[CH:27][C:26]=1[CH3:34].C(N(CC)CC)C>C(O)(C)C>[Si:1]([O:8][C@@H:9]1[C@@H:14]([CH3:15])[CH2:13][N:12]([C:25]2[C:30]([N+:31]([O-:33])=[O:32])=[CH:29][N:28]=[CH:27][C:26]=2[CH3:34])[CH2:11][C@H:10]1[NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 588823714-Chloro-3-methyl-5-nitropyridine2×HCID 70901078tert-Butyl N-[(3R,4R,5S)-4-[(tert-butyldimethylsilyl)oxy]-5-methylpiperidin-3-yl]carbamate

Product 1

HCID 86726885tert-Butyl [(3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methyl-1-(3-methyl-5-nitropyridin-4-yl)piperidin-3-yl]carbamateYield 37.3%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of tert-butyl ((3R,4R,5S)-4-{[tert-butyl(dimethyl)silyl]oxy}-5-methylpiperidin-3-yl)carbamate (23 mg, 0.067 mmol, Example 26, Step 7), 4-chloro-3-methyl-5-nitropyridine (from ACES Pharma, 16 mg, 0.096 mmol), and triethylamine (37 μL, 0.27 mmol) in isopropyl alcohol (0.60 mL) was heated at 75° C. in a sealed vial for 16 h. Another portion of 4-chloro-3-methyl-5-nitropyridine (19 mg) was added and stirring was continued for 2 days at 100° C. The crude reaction mixture was purified by flash chromatography (24 g silica gel column, eluting with 0-100% EtOAc/hexanes) to afford the sub-title compound (12 mg, 37% yield). LCMS (ESI) calc. for C23H41N4O5Si [M+H]+: m/z=481.3. found 481.3.

Workup

  1. customThe crude reaction mixture
  2. customwas purified by flash chromatography (24 g silica gel column, eluting with 0-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-b41426e255874bce92683db67b976af9
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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