Sodium Thiosulfate → ter t-butyl [(3S,5R)-1-(3-nitro-1-oxido-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)-5-(trifluoromethyl)piperidin-3-yl]carbamate

HRID 1499620Notes

Reaction equation

HRID 1499620 reaction equation
C1C=C(Cl)C=C(C(OO)=[O:9])C=1.[N+:12]([C:15]1[C:16]([N:24]2[CH2:29][C@H:28]([C:30]([F:33])([F:32])[F:31])[CH2:27][C@H:26]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH2:25]2)=[C:17]2[CH2:23][CH2:22][CH2:21][C:18]2=[N:19][CH:20]=1)([O-:14])=[O:13].[O-]S([O-])(=S)=O.[Na+].[Na+]>C(Cl)Cl>[N+:12]([C:15]1[C:16]([N:24]2[CH2:29][C@H:28]([C:30]([F:33])([F:32])[F:31])[CH2:27][C@H:26]([NH:34][C:35](=[O:41])[O:36][C:37]([CH3:38])([CH3:40])[CH3:39])[CH2:25]2)=[C:17]2[CH2:23][CH2:22][CH2:21][C:18]2=[N+:19]([O-:9])[CH:20]=1)([O-:14])=[O:13]

Participants

5

Reactant 3

HCID 24477Sodium ThiosulfateHCID 70297m-Chloroperbenzoic acidHCID 86726741HCID 86726741, compound

Product 1

HCID 86726742ter t-butyl [(3S,5R)-1-(3-nitro-1-oxido-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)-5-(trifluoromethyl)piperidin-3-yl]carbamateYield 60.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

mCPBA (0.16 g, 0.93 mmol) was added to a solution of tert-butyl [(3S,5R)-1-(3-nitro-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl)-5-(trifluoromethyl)piperidin-3-yl]carbamate (0.16 g, 0.37 mmol) (second peak, pure product resolved on chiral HPLC from previous step) in DCM (2.0 mL) at room temperature. The reaction mixture was stirred at room temperature for 2 h. The mixture was treated with aq. Na2S2O3, then 1 M NaOH, and extracted with EtOAc. The combined organic layers were concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using CombiFlash® apparatus (20 g column) eluting with 0-100% EtOAc in hexanes followed by MeOH/EtOAc (0-30%) to give 0.10 g (60%) of the sub-title compound as a reddish solid. 0.033 g of unreacted starting material was recovered. LCMS calc. for C19H26F3N4O5 (M+H)+ m/z=447.2. found: 446.9.

Workup

  1. extraction1 M NaOH, and extracted with EtOAc
  2. concentrationThe combined organic layers were concentrated under reduced pressure
  3. customThe residue was purified by column chromatography on silica gel using CombiFlash® apparatus (20 g column)
  4. washeluting with 0-100% EtOAc in hexanes

Sources & evidence

ORD record
ord-371bc18f522d42ecabdf77695413d181
Source dataset
uspto-grants-2015_12
Patent number
US09200004B2

Reaction notes

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