Sodium hydride → (S)-tert-butyl 3-((8-chloro-3-cyanoisoquinolin-1-yl)oxy)pyrrolidine-1-carboxylate

HRID 1476897Notes

Reaction equation

HRID 1476897 reaction equation
[OH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[H-].[Na+].Cl[C:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][C:25]=2[Cl:27])[CH:20]=[C:19]([C:28]#[N:29])[N:18]=1>C1COCC1>[Cl:27][C:25]1[CH:24]=[CH:23][CH:22]=[C:21]2[C:26]=1[C:17]([O:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1)=[N:18][C:19]([C:28]#[N:29])=[CH:20]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 854055tert-Butyl (3S)-3-hydroxypyrrolidine-1-carboxylateHCID 903870031,8-Dichloroisoquinoline-3-carbonitrile

Product 1

HCID 90387316(S)-tert-butyl 3-((8-chloro-3-cyanoisoquinolin-1-yl)oxy)pyrrolidine-1-carboxylateYield 73.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-tert-butyl 3-hydroxypyrrolidine-1-carboxylate (126 mg, 0.674 mmol) in THF (5 mL) was added NaH (26.8 mg, 0.677 mmol) at 0° C. The mixture was stirred for 30 minutes. Next, 1,8-dichloroisoquinoline-3-carbonitrile was added and the reaction mixture was warmed to RT for 4 hours. The reaction was quenched with H2O (2 mL) and the mixture was extracted with EtOAc (3×10 mL). The organic layers were combined and concentrated in vacuo. The crude product was purified by preparative TLC to give the title compound (120 mg, 73.2%).

Workup

  1. customThe reaction was quenched with H2O (2 mL)
  2. extractionthe mixture was extracted with EtOAc (3×10 mL)
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by preparative TLC

Sources & evidence

ORD record
ord-2bcf5beda0a04b6ca33c803226f34b1f
Source dataset
uspto-grants-2016_08
Patent number
US09402841B2

Reaction notes

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