Acetic Anhydride → 4-[(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-(trifluoromethyl)piperidin-1-yl]-3-nitro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetate

HRID 1499512Notes

Reaction equation

HRID 1499512 reaction equation
[N+:1]([C:4]1[C:5]([N:14]2[CH2:19][C@H:18]([C:20]([F:23])([F:22])[F:21])[CH2:17][C@H:16]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:15]2)=[C:6]2[CH2:13][CH2:12][CH2:11][C:7]2=[N+:8]([O-])[CH:9]=1)([O-:3])=[O:2].[CH3:32][C:33]([O:35]C(C)=O)=[O:34]>>[C:33]([O:35][CH:11]1[C:7]2=[N:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[C:5]([N:14]3[CH2:19][C@H:18]([C:20]([F:21])([F:23])[F:22])[CH2:17][C@H:16]([NH:24][C:25]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:31])[CH2:15]3)=[C:6]2[CH2:13][CH2:12]1)(=[O:34])[CH3:32]

Participants

3

Reactant 2

HCID 7918Acetic AnhydrideHCID 86726742ter t-butyl [(3S,5R)-1-(3-nitro-1-oxido-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)-5-(trifluoromethyl)piperidin-3-yl]carbamate

Product 1

HCID 867267444-[(3S,5R)-3-[(tert-butoxycarbonyl)amino]-5-(trifluoromethyl)piperidin-1-yl]-3-nitro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-yl acetateYield 74%

Conditions

Temperature
90 °C

Procedure

To tert-butyl [(3S,5R)-1-(3-nitro-1-oxido-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)-5-(trifluoromethyl)piperidin-3-yl]carbamate (114.7 mg, 0.2569 mmol) was added Ac2O (2.0 mL, 21 mmol). The reaction mixture was heated at 90° C. for 1 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was diluted with DCM, and poured into a saturated aqueous solution of Na2CO3 at 0° C. The separated aqueous layer was further extracted with DCM (3 times). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by chromatography on silica gel (0-100% EtOAc in hexanes) to give the sub-title compound as a brown foamy solid (92.3 mg, 74%). LCMS calc. for C21H28F3N4O6 (M+H)+: m/z=489.2. found 489.2.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. additionThe residue was diluted with DCM
  4. additionpoured into a saturated aqueous solution of Na2CO3 at 0° C
  5. extractionThe separated aqueous layer was further extracted with DCM (3 times)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by chromatography on silica gel (0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-726b76dc04834b39bf763c234a8b7128
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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