Sodium Hydroxide → HCID 59004638, compound

HRID 1668472Notes

Reaction equation

HRID 1668472 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)=[C:6]([C:8](=O)[CH2:9]Cl)[CH:7]=1.[OH-].[Na+].[BH4-].[Na+]>C(O)C>[Br:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[N:12]([CH:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1)[CH:9]=[CH:8]2

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 45117931HCID 45117931, compound

Product 1

HCID 59004638HCID 59004638, compoundYield 59.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To an ice cold solution of compound 79 (583 mg, 1.526 mmol) in 95% ethanol (25 mL) was added 1M sodium hydroxide (1.526 mL, 1.526 mmol) followed by sodium borohydride (28.9 mg, 0.763 mmol) and the mixture stirred under ice cooling for 45 minutes. The reaction was quenched with ice cold H2O (25 mL), diluted with CH2Cl2, transferred to a separatory funnel and the organic layer separated. The aqueous layer was further extracted with CH2Cl2 (twice) and the combined organic layers washed with brine, dried over sodium sulfate and concentrated to residue. The residue was taken up in anhydrous dioxane (25 mL) and heated to reflux for 3 hours. After cooling to room temperature the reaction was treated with ice-cold 2N potassium carbonate, diluted with CH2Cl2, transferred to a separatory funnel and the organic layer separated. The aqueous layer was further extracted with CH2Cl2 (twice) and the combined organic layers washed with water (twice), brine, dried over sodium sulfate concentrated under reduced pressure and the residue purified via chromatography on silica gel (2M NH3 in methanol:CH2Cl2 2.5:97.5 to 5:95) to yield an off white solid, 80 (265 mg, 59.3%). 1H NMR (DMSO-d6) δ 1.83-1.93 (m, 2H), 1.95-2.04 (m, 2H), 2.13 (dt, 2H, J=11.5, 2.2 Hz), 2.23 (s, 3H), 2.89 (d, 2H, J=11.4 Hz), 4.28-4.35 (m, 1H), 6.44 (d, 1H, J=3.1 Hz), 7.22 (dd, 1H, J=8.7, 1.8 Hz), 7.51-7.56 (m, 2H), 7.72 (d, 1H, J=1.9 Hz); ESI-MS (m/z, %): 293/295 (MH+, 100%).

Workup

  1. customThe reaction was quenched with ice cold H2O (25 mL)
  2. additiondiluted with CH2Cl2
  3. customtransferred to a separatory funnel
  4. customthe organic layer separated
  5. extractionThe aqueous layer was further extracted with CH2Cl2 (twice) and the combined organic layers
  6. washwashed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated to residue
  9. temperatureheated
  10. temperatureto reflux for 3 hours
  11. additionwas treated with ice-cold 2N potassium carbonate
  12. additiondiluted with CH2Cl2
  13. customtransferred to a separatory funnel
  14. customthe organic layer separated
  15. extractionThe aqueous layer was further extracted with CH2Cl2 (twice) and the combined organic layers
  16. washwashed with water (twice), brine
  17. dry with materialdried over sodium sulfate
  18. concentrationconcentrated under reduced pressure
  19. customthe residue purified via chromatography on silica gel (2M NH3 in methanol:CH2Cl2 2.5:97.5 to 5:95)

Sources & evidence

ORD record
ord-7e5ad35f10bd4bfc9dcc74e9bce37f59
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

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