Hydrochloric Acid → HCID 58137281, compound

HRID 1424581Notes

Reaction equation

HRID 1424581 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:22]=1[C:9]1([CH:14]=[CH:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1)[N:8]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1)[C:7]2=[O:32].Cl.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>O=[Pt]=O.CC#N>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:22]=1[C:9]1([CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]1)[N:8]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1)[C:7]2=[O:32]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 90495Di-tert-butyl dicarbonateHCID 58137323HCID 58137323, compound

Product 1

HCID 58137281HCID 58137281, compound

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 6342AcetonitrileSolvent

Procedure

Tert-butyl 7-chloro-2-(4-methoxybenzyl)-3-oxo-2′,3′-dihydro-1′H-spiro[isoindoline-1,4′-pyridine]-1′-carboxylate (1.69 g, 3.71 mmol, 1.0 equiv) and PtO2 (100 mg, 0.440 mmol, 12 mol %) were added to a solution of 1:1 4.0 M HCl:MeCN (200 mL). The mixture was transferred to a Parr hydrogenation vessel and hydrogenated at 55 psi for 3 d. After this time the vessel was vented and the pale yellow solution filtered through a bed of Celite. The mixture was evaporated and the residue was dissolved in 1:1 MeCN:10% aq K2CO3 (200 mL); Boc2O (1.21 g, 5.56 mmol, 1.5 equiv) was added and the mixture was stirred for 17 h. After this time the solution was evaporated and the residue was diluted with EtOAc. The organic layer was washed with 1.0 M aq HCl and brine, dried over Na2SO4, and evaporated. The reduced product was purified by flash chromatography on silica gel, eluting with 20-80% EtOAc in hexanes. Tert-butyl 7-chloro-2-(4-methoxybenzyl)-3-oxospiro[isoindoline-1,4′-piperidine]-1′-carboxylate was isolated as a pale yellow foam (0.702 g, 1.54 mmol, 42%).

Workup

  1. filtrationthe pale yellow solution filtered through a bed of Celite
  2. customThe mixture was evaporated
  3. dissolutionthe residue was dissolved in 1:1 MeCN
  4. customAfter this time the solution was evaporated
  5. additionthe residue was diluted with EtOAc
  6. washThe organic layer was washed with 1.0 M aq HCl and brine
  7. dry with materialdried over Na2SO4
  8. customevaporated
  9. customThe reduced product was purified by flash chromatography on silica gel
  10. washeluting with 20-80% EtOAc in hexanes

Sources & evidence

ORD record
ord-24356cf3a4d8454a8d22ef8496f82b47
Source dataset
uspto-grants-2015_01
Patent number
US08927715B2

Reaction notes

Loading…