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

HRID 1924362Notes

Reaction equation

HRID 1924362 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, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolvent

Procedure

To a 0.2 mM solution of trans 4-hydroxy L-BOC-proline (1 eq) in DMSO 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 sat. aq. citric acid 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. The solid was dissolved in MeOH and to the stirred solution an excess (4 eq) of 2.0 M trimethylsilyldiazomethane in hexanes 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 (SiO2, PE/EtOAc 8/2 v/v as eluent) to give title product as a solid. MS (ES+) C20H23BrN2O5 requires 451. Found: 452 (M+H+).

Workup

  1. temperaturecooled to 10° C.
  2. temperatureto warm to RT
  3. stirringstirred overnight
  4. washThe organic layer was washed with sat. aq. citric acid 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. additionwas added dropwise at 15° C
  10. stirringThe resulting mixture was stirred for 15 min after gas evolution
  11. customVolatiles were removed by rotary evaporation
  12. customthe residue was purified by flash chromatography (SiO2, PE/EtOAc 8/2 v/v as eluent)

Sources & evidence

ORD record
ord-041af2edd1534cb8a14b2ca606e38eb1
Source dataset
uspto-grants-2012_05
Patent number
US08178520B2

Reaction notes

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