Sodium Hydroxide → HCID 59004637, compound

HRID 1668488Notes

Reaction equation

HRID 1668488 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:12][CH2:13][C@@H:14]2[CH2:18][CH2:17][CH2:16][N:15]2[CH3:19])=[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]([CH2:13][C@@H:14]1[CH2:18][CH2:17][CH2:16][N:15]1[CH3:19])[CH:9]=[CH:8]2

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 59004651HCID 59004651, compound

Product 1

HCID 59004637HCID 59004637, compoundYield 35.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To an ice cold solution of compound 101 (402 mg, 1.052 mmol) in 95% ethanol (20 mL) was added 1M sodium hydroxide (1.052 mL, 1.052 mmol) followed by sodium borohydride (19.9 mg, 0.526 mmol) and the mixture stirred under ice cooling for 45 minutes. The reaction was quenched with ice cold H2O (5 mL), diluted with dichloromethane, transferred to a separatory funnel and the organic layer separated. The aqueous layer was further extracted with dichloromethane (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 (20 mL) and heated to reflux for 2.5 hours. After cooling to room temperature the reaction was treated with ice-cold 2N potassium carbonate, diluted with dichloromethane, transferred to a separatory funnel and the organic layer separated. The aqueous layer was further extracted with dichloromethane (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 (MeOH:CH2Cl2, 3:97) to yield compound 102 (110 mg, 35.7%) as a yellow oil. 1H NMR (DMSO-d6) δ 1.42-1.50 (m, 1H), 1.50-1.60 (m, 2H), 1.62-1.71 (m, 1H), 2.09-2.14 (m, 1H), 2.17 (s, 3H), 2.50-2.57 (m, 1H), 2.90-2.96 (m, 1H), 4.05 (dd, 1H, J=14.1, 6.3 Hz), 4.23 (dd, 1H, J=14.0, 5.1 Hz), 6.41 (d, 1H, J=3.0 Hz), 7.22 (dd, 1H, J=8.9, 1.9 Hz), 7.42-7.49 (m, 2H), 7.71 (d, 1H, J=2.0 Hz); ESI-MS (m/z, %): 293/295 (MH+, 100%).

Workup

  1. customThe reaction was quenched with ice cold H2O (5 mL)
  2. additiondiluted with dichloromethane
  3. customtransferred to a separatory funnel
  4. customthe organic layer separated
  5. extractionThe aqueous layer was further extracted with dichloromethane (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 2.5 hours
  11. additionwas treated with ice-cold 2N potassium carbonate
  12. additiondiluted with dichloromethane
  13. customtransferred to a separatory funnel
  14. customthe organic layer separated
  15. extractionThe aqueous layer was further extracted with dichloromethane (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 (MeOH:CH2Cl2, 3:97)

Sources & evidence

ORD record
ord-5a528023085f4e6a944b8b2db7fa6979
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

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