Acetyl chloride → 4-{(3R,4R,5S)-4-(Acetyloxy)-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}-3-nitro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

HRID 1499494Notes

Reaction equation

HRID 1499494 reaction equation
[CH3:1][C:2]([O:4][C:5]([CH3:7])=[O:6])=O.[OH:8][C@@H:9]1[C@@H:14]([CH3:15])[CH2:13][N:12]([C:16]2[C:21]([N+:22]([O-:24])=[O:23])=[CH:20][N+:19]([O-])=[C:18]3CC[CH2:28][C:17]=23)[CH2:11][C@H:10]1[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33].[C:37](Cl)(=[O:39])[CH3:38].CCN(C(C)C)C(C)C>>[C:5]([O:4][CH:2]1[C:18]2=[N:19][CH:20]=[C:21]([N+:22]([O-:24])=[O:23])[C:16]([N:12]3[CH2:13][C@H:14]([CH3:15])[C@@H:9]([O:8][C:37](=[O:39])[CH3:38])[C@H:10]([NH:29][C:30]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:36])[CH2:11]3)=[C:17]2[CH2:28][CH2:1]1)(=[O:6])[CH3:7]

Participants

5

Reactant 4

HCID 6367Acetyl chlorideHCID 7918Acetic AnhydrideHCID 81531DiisopropylethylamineHCID 86726723tert-Butyl [(3R,4R,5S)-4-hydroxy-5-methyl-1-(3-nitro-1-oxido-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)piperidin-3-yl]carbamate

Product 1

HCID 867267244-{(3R,4R,5S)-4-(Acetyloxy)-3-[(tert-butoxycarbonyl)amino]-5-methylpiperidin-1-yl}-3-nitro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetateYield 79%

Conditions

Temperature
90 °C

Procedure

Ac2O (2.0 mL, 21 mmol) was added to tert-butyl [(3R,4R,5S)-4-hydroxy-5-methyl-1-(3-nitro-1-oxido-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)piperidin-3-yl]carbamate (0.090 g, 0.22 mmol) in a tube that was then sealed. The reaction mixture was heated in the sealed tube with stirring in an oil bath at 90° C. oil bath. The reaction mixture was allowed to cool to room temperature and acetyl chloride (0.10 mL) and DIPEA (0.2 mL) were then added. The resulting mixture was stirred at room temperature for 15 min. After removal of the solvents under reduced pressure, the resulting residue was diluted with EtOAc and aq. Na2CO3 and stirred at room temperature for 30 min. The organic layer was separated, dried and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluting with 0-70% EtOAc in hexanes) to give the sub-title compound (86 mg, 79%) as a foamy brown powder. LCMS calc. for C23H33N4O8 (M+1)+: m/z=493.2. Found: 493.2.

Workup

  1. customwas then sealed
  2. temperatureThe reaction mixture was heated in the sealed tube
  3. temperatureto cool to room temperature
  4. stirringThe resulting mixture was stirred at room temperature for 15 min
  5. customAfter removal of the solvents under reduced pressure
  6. additionthe resulting residue was diluted with EtOAc and aq. Na2CO3
  7. stirringstirred at room temperature for 30 min
  8. customThe organic layer was separated
  9. customdried
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue was purified by silica gel column chromatography (eluting with 0-70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-eb9e2ce82a954c84b21b7557e30b588d
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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