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 1499621Notes

Reaction equation

HRID 1499621 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 78%

Conditions

Temperature
90 °C

Procedure

A mixture of tert-butyl [(3S,5R)-1-(3-nitro-1-oxido-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)-5-(trifluoromethyl)piperidin-3-yl]carbamate (0.100 g, 0.224 mmol) in Ac2O (1.5 mL, 16 mmol) was stirred at 90° C. for 1 h. The solution was allowed to cool to room temperature, then concentrated under reduced pressure at 60° C. The residue was diluted with EtOAc (5 mL), washed quickly with 1N NaOH. The aqueous phase was extracted with EtOAc twice. The combined organic phases were condensed and columned on 20 g silica gel, eluting with 0-50% EtOAc in hexanes to give the sub-title compound as a brown solid (0.085 g, 78%). LCMS calc. for C21H28F3N4O6 (M+H)+ m/z=489.2. found: 489.0.

Workup

  1. temperatureto cool to room temperature
  2. concentrationconcentrated under reduced pressure at 60° C
  3. additionThe residue was diluted with EtOAc (5 mL)
  4. washwashed quickly with 1N NaOH
  5. extractionThe aqueous phase was extracted with EtOAc twice
  6. customcondensed
  7. washeluting with 0-50% EtOAc in hexanes

Sources & evidence

ORD record
ord-46a2222df0c84f85ad97ea13dd2c175c
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

Loading…