Sodium hydride → [1-(1-Chloro-6-methoxyisoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]-carbamic acid tert-butyl ester

HRID 651603Notes

Reaction equation

HRID 651603 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:16])[NH:9][C@H:10]1[CH2:14][CH2:13][NH:12][C:11]1=[O:15])([CH3:6])([CH3:5])[CH3:4].Br[CH2:18][C:19]1[CH:28]=[C:27]2[C:22]([CH:23]=[CH:24][N:25]=[C:26]2[Cl:29])=[CH:21][C:20]=1[O:30][CH3:31]>C1COCC1.C1COCC1.CN(C=O)C>[C:3]([O:7][C:8](=[O:16])[NH:9][C@H:10]1[CH2:14][CH2:13][N:12]([CH2:18][C:19]2[CH:28]=[C:27]3[C:22]([CH:23]=[CH:24][N:25]=[C:26]3[Cl:29])=[CH:21][C:20]=2[O:30][CH3:31])[C:11]1=[O:15])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 10750535(S)-tert-Butyl (2-oxopyrrolidin-3-yl)carbamateHCID 181763157-(Bromomethyl)-1-chloro-6-methoxyisoquinoline

Product 1

HCID 54569475[1-(1-Chloro-6-methoxyisoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]-carbamic acid tert-butyl esterYield 42.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

Sodium hydride (0.057 g, 1.4 mmol, 60% mineral oil dispersion) is suspended in anhydrous THF (5 mL) and treated with a solution of (2-oxopyrrolidin-3-(S)-yl)-carbamic acid tert-butyl ester (0.223 g, 1.1 mmol) and 7-bromomethyl-1-chloro-6-methoxy-isoquinoline (0.32 g, 1.1 mmol) in THF/DMF (10 mL, 6:1) at 0° C. The reaction mixture is warmed to ambient temperature, stirred for 3 hours, quenched by the addition of saturated NH4Cl and diluted with EtOAc. The layers are separated. The organic layer is washed with saturated NaCl, dried over Na2SO4, filtered, and concentrated to give a white solid. The solid is collected, washed with a small amount of EtOAc and copious amounts of Et2O to yield the title compound (0.18 g, 0.47 mmol).

Workup

  1. customquenched by the addition of saturated NH4Cl
  2. additiondiluted with EtOAc
  3. customThe layers are separated
  4. washThe organic layer is washed with saturated NaCl
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a white solid
  9. customThe solid is collected
  10. washwashed with a small amount of EtOAc and copious amounts of Et2O

Sources & evidence

ORD record
ord-3a124869057c4249915076bc20141752
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

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