Sodium hydride → HCID 20680633, compound

HRID 651643Notes

Reaction equation

HRID 651643 reaction equation
C([O:8][C:9](=[O:17])[NH:10][C@H:11]1[CH2:15][CH2:14][NH:13][C:12]1=[O:16])C1C=CC=CC=1.[H-].[Na+].O([C:27]1[C:36]2[C:31](=[CH:32][C:33]([CH2:37]Br)=[CH:34][CH:35]=2)[CH:30]=[CH:29][N:28]=1)C1C=CC=CC=1.[NH4+].[Cl-:40]>C1COCC1.C(Cl)Cl.CN(C=O)C>[Cl:40][C:27]1[C:36]2[C:31](=[CH:32][C:33]([CH2:37][N:13]3[CH2:14][CH2:15][C@H:11]([NH:10][C:9](=[O:17])[OH:8])[C:12]3=[O:16])=[CH:34][CH:35]=2)[CH:30]=[CH:29][N:28]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 11447643Benzyl [(3S)-2-oxopyrrolidin-3-yl]carbamateHCID 181763341-Phenoxy-6-bromomethyl-isoquinoline

Product 1

HCID 20680633HCID 20680633, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (2-oxopyrrolidin-3-(S)-yl)-carbamic acid benzyl ester (0.15 g, 0.64 mmol) in 6 mL of 10:1 THF:DMF at 0° C. is added a 60% NaH dispersion (0.03 g, 0.71 mmol) followed by 1-phenoxy-6-bromomethyl-isoquinoline (0.2 g, 0.64 mmol). After 16 hours, the solution is treated with 10 mL of saturated NH4Cl. The solution is diluted with CH2Cl2. The organic layer is washed with H2O and saturated NaCl. The resulting product is suspended in 5 g of NH4OAc and heated to 120° C. After 36 hours, the solution is cooled to ambient temperatures. The solution is diluted with H2O and CH2Cl2. The organic layer is washed with H2O and saturated NaCl. The organic layer is dried over MgSO4, filtered and concentrated. The residue is purified by column chromatography eluting with 5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2 to give the product as a white solid (0.043 g, 0.11 mmol).

Workup

  1. washThe organic layer is washed with H2O and saturated NaCl
  2. waitAfter 36 hours
  3. temperaturethe solution is cooled to ambient temperatures
  4. additionThe solution is diluted with H2O and CH2Cl2
  5. washThe organic layer is washed with H2O and saturated NaCl
  6. dry with materialThe organic layer is dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is purified by column chromatography
  10. washeluting with 5% MeOH/CH2Cl2 to 10% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-d4dfe35deb2b497aadc93d977e51db71
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

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