(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid → (4R)-4-[(7-bromo-6-methoxyisoquinolin-1-yl)oxy]-1-(tert-butoxycarbonyl)-L-proline

HRID 2045704Notes

Reaction equation

HRID 2045704 reaction equation
CC(C)([O-])C.[K+].[OH:7][C@H:8]1[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:10]([C:20]([OH:22])=[O:21])[CH2:9]1.[Br:23][C:24]1[CH:33]=[C:32]2[C:27]([CH:28]=[CH:29][N:30]=[C:31]2Cl)=[CH:26][C:25]=1[O:35][CH3:36]>CS(C)=O>[Br:23][C:24]1[CH:33]=[C:32]2[C:27]([CH:28]=[CH:29][N:30]=[C:31]2[O:7][C@H:8]2[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[C@H:10]([C:20]([OH:22])=[O:21])[CH2:9]2)=[CH:26][C:25]=1[O:35][CH3:36]

Participants

5

Reactant 3

HCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acidHCID 23665647Potassium tert-butoxideHCID 595711467-Bromo-1-chloro-6-methoxyisoquinoline

Product 1

HCID 58005163(4R)-4-[(7-bromo-6-methoxyisoquinolin-1-yl)oxy]-1-(tert-butoxycarbonyl)-L-proline

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

Potassium tert-butoxide (14.1 g, 125 mmol) was added to a solution of trans 4-hydroxy L-BOC-proline (9.67 g, 41.8 mmol) in DMSO (180 mL) at RT. The reaction mixture was stirred at RT for 30 min and cooled to 15° C. The product from step 3 (11.4 g, 41.8 mmol) was added to the reaction mixture as a solution in DMSO (45 mL); the reaction mixture was allowed to warm to RT and stirred for 30 min. The reaction mixture was quenched with ice-cold 10% citric acid solution and partitioned with EtOAc. The organic layer was washed with aqueous citric acid solution, water and brine, and the aqueous phases were back-extracted with EtOAc. The combined organic phases were dried over anhydrous Na2SO4, and the solvent was evaporated. LRMS ESI+ (M+H-tBu)+411.2.

Workup

  1. temperaturecooled to 15° C
  2. temperatureto warm to RT
  3. stirringstirred for 30 min
  4. customThe reaction mixture was quenched with ice-cold 10% citric acid solution
  5. custompartitioned with EtOAc
  6. washThe organic layer was washed with aqueous citric acid solution, water and brine
  7. extractionthe aqueous phases were back-extracted with EtOAc
  8. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  9. customthe solvent was evaporated

Sources & evidence

ORD record
ord-7945c864184c4afba2d1734ba3d42ffa
Source dataset
uspto-grants-2013_11
Patent number
US08591878B2

Reaction notes

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