(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid → HCID 58005112, compound

HRID 1879251Notes

Reaction equation

HRID 1879251 reaction equation
[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([OH:16])=[O:15])[CH2:3]1.[C:17](O[K])(C)(C)C.[Br:23][C:24]1[CH:33]=[C:32]2[C:27]([CH:28]=[CH:29][N:30]=[C:31]2Cl)=[CH:26][CH:25]=1.C[Si](C=[N+]=[N-])(C)C>CS(C)=O.CO>[Br:23][C:24]1[CH:33]=[C:32]2[C:27]([CH:28]=[CH:29][N:30]=[C:31]2[O:1][C@H:2]2[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]2)=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acidHCID 167693TrimethylsilyldiazomethaneHCID 65020247-Bromo-1-ChloroisoquinolineHCID 178418922HCID 178418922, compound

Product 1

HCID 58005112HCID 58005112, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Procedure

To a solution of trans 4-hydroxy L-BOC-proline (1 eq) in DMSO (0.2 M) at RT was added tBuOK (3 eq) in a single portion. The reaction mixture was stirred at RT for 30 min, cooled to 10° C. and 7-bromo-1-chloroisoquinoline was added (1 eq). The resulting mixture was allowed to warm to RT and stirred overnight. The organic layer was washed with citric acid 10% solution, water and brine and the aqueous phases were back extracted with EtOAc. The combined organic phases were dried (Na2SO4) and the solvent evaporated under reduced pressure to give a dark solid that was dissolved in MeOH. To the stirred solution, trimethylsilyldiazomethane 2.0 M in hexanes (4.0 eq.) was added dropwise at 15° C. The resulting mixture was stirred for 15 min after gas evolution has ceased. Volatiles were removed by rotary evaporation and the residue was purified by flash chromatography (HORIZON system, column SiO2, eluent: PE:EtOAc with EtOAc (from 60 to 80%) to give the title product 85 as a solid (71%). MS (ES+) m/z 452 (M+H+).

Workup

  1. temperaturecooled to 10° C.
  2. temperatureto warm to RT
  3. stirringstirred overnight
  4. washThe organic layer was washed with citric acid 10% solution, water and brine
  5. extractionthe aqueous phases were back extracted with EtOAc
  6. dry with materialThe combined organic phases were dried (Na2SO4)
  7. customthe solvent evaporated under reduced pressure
  8. customto give a dark solid
  9. stirringThe resulting mixture was stirred for 15 min after gas evolution
  10. customVolatiles were removed by rotary evaporation
  11. customthe residue was purified by flash chromatography (HORIZON system, column SiO2, eluent

Sources & evidence

ORD record
ord-fdca1237f06147dd9a71220a438e16ea
Source dataset
uspto-grants-2012_11
Patent number
US08314062B2

Reaction notes

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