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

HRID 2192597Notes

Reaction equation

HRID 2192597 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].CCN(C(C)C)C(C)C.Cl[C:34]1[CH:39]=[CH:38][N:37]=[CH:36][C:35]=1[N+:40]([O-:42])=[O:41]>CC(O)C>[Si:1]([O:8][C@@H:9]1[C@@H:14]([CH3:15])[CH2:13][N:12]([C:34]2[CH:39]=[CH:38][N:37]=[CH:36][C:35]=2[N+:40]([O-:42])=[O:41])[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 81531DiisopropylethylamineHCID 27357814-Chloro-3-nitropyridineHCID 70901078tert-Butyl N-[(3R,4R,5S)-4-[(tert-butyldimethylsilyl)oxy]-5-methylpiperidin-3-yl]carbamate

Product 1

HCID 59226604tert-butyl (3R,4R,5S)-4-(tert-butyldimethylsilyloxy)-5-methyl-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamateYield 76%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl (3R,4R,5S)-4-(tert-butyldimethylsilyloxy)-5-methylpiperidin-3-ylcarbamate (1.0 equiv.) in i-PrOH (0.09 M) was added DIEA (2.5 equiv.) and 4-chloro-3-nitropyridine (1.5 equiv.). The reaction mixture was stirred at 60° C. for 2 hours. The volatiles were removed under vacuo, the residue was diluted with ethyl acetate and washed with sat. NaCl. The organic phase was dried with magnesium sulfate, filtered, and concentrated. The crude material was purified by silica gel column chromatography eluting with ethyl acetate and hexanes (1:2) to give tert-butyl (3R,4R,5S)-4-(tert-butyldimethylsilyloxy)-5-methyl-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamate in 76% yield. LC/MS=467.3 (M+H), Rt=1.09 min.

Workup

  1. customThe volatiles were removed under vacuo
  2. additionthe residue was diluted with ethyl acetate
  3. washwashed with sat. NaCl
  4. dry with materialThe organic phase was dried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by silica gel column chromatography
  8. washeluting with ethyl acetate and hexanes (1:2)

Sources & evidence

ORD record
ord-1aa336c7118741ab8134c39fc8bc7bed
Source dataset
uspto-grants-2012_12
Patent number
US08329732B2

Reaction notes

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