Sodium hydride → HCID 68694119, compound

HRID 1296293Notes

Reaction equation

HRID 1296293 reaction equation
[H-].[Na+].[O:3]=[C:4]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][C@H:6]([C:14]([O:16][CH3:17])=[O:15])[NH:5]1.Br[CH:19]([CH3:24])[C:20]([O:22][CH3:23])=[O:21]>CN(C=O)C>[CH3:23][O:22][C:20](=[O:21])[CH:19]([N:5]1[CH:6]([C:14]([O:16][CH3:17])=[O:15])[CH2:7][C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:4]1=[O:3])[CH3:24]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 95576Methyl 2-bromopropionateHCID 11171741HCID 11171741, compound

Product 1

HCID 68694119HCID 68694119, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% oil dispersion, 0.51 g, 12.4 mmol) was added to a stirring solution of (R)-methyl 1-oxo-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (1.3 g, 6.2 mmol) in DMF (13 ml). After stirring for 30 min at ambient temperature, methyl 2-bromopropionate (1.1 ml, 9.3 mmol) was added. After stirring at 40° C. for 2 h, the reaction was removed from the heat and quenched with water. The reaction mixture was transferred to a separatory funnel with EtOAc/water. Extraction with EtOAc (2×) and washing the combined organic layers with saturated NaHCO3, water, and brine and drying over MgSO4 afforded 2.0 g of crude product after evaporation of the solvent. Flash chromatography (SiO2, hexanes to 80% EtOAc in hexanes) afforded Isomer A (0.53 g, 29% yield), Isomer B (0.28 g, 15% yield) and a mixture of the two isomers (0.28 g, 15% yield). All have MS (ESI) 292 (M+H).

Workup

  1. stirringAfter stirring at 40° C. for 2 h
  2. customthe reaction was removed from the
  3. temperatureheat
  4. customquenched with water
  5. customThe reaction mixture was transferred to a separatory funnel with EtOAc/water
  6. extractionExtraction with EtOAc (2×)
  7. washwashing the combined organic layers with saturated NaHCO3, water, and brine
  8. dry with materialdrying over MgSO4
  9. customafforded 2.0 g of crude product
  10. customafter evaporation of the solvent
  11. customFlash chromatography (SiO2, hexanes to 80% EtOAc in hexanes) afforded Isomer A (0.53 g, 29% yield), Isomer B (0.28 g, 15% yield)
  12. additiona mixture of the two isomers (0.28 g, 15% yield)

Sources & evidence

ORD record
ord-21e4a752d11c494682d492d505a759d3
Source dataset
uspto-grants-2007_07
Patent number
US07244843B2

Reaction notes

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