Water → HCID 22141370, compound

HRID 428885Notes

Reaction equation

HRID 428885 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][C:12]([N:14]2[CH2:19][CH:18]3[CH:16]([C:17]3([C:21]3[CH:22]=[C:23]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])[CH:24]=[CH:25][CH:26]=3)[CH3:20])[CH2:15]2)=O)=[CH:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][CH2:12][N:14]2[CH2:15][CH:16]3[CH:18]([C:17]3([C:21]3[CH:22]=[C:23]([NH:27][S:28]([CH3:31])(=[O:29])=[O:30])[CH:24]=[CH:25][CH:26]=3)[CH3:20])[CH2:19]2)=[CH:2]1

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 21226445Aluminium lithium hydrideHCID 22141354HCID 22141354, compound

Product 1

HCID 22141370HCID 22141370, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(3-{3-[3-(IH-indol-3-yl)propanoyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide (Preparation 123, 135 mg, 0.34 mmol) in anhydrous tetrahydrofuran (2.5 ml) under a nitrogen atmosphere at 0° C. was added dropwise lithium aluminium hydride (1.0M solution in tetrahydrofuran, 0.68 ml, 0.68 mmol) and the mixture was stirred at room temperature for 20 h. The rapidly stirred reaction mixture was treated sequentially with water (0.68 ml), sodium hydrogen carbonate (400 mg) and ethyl acetate (15 ml). After 30 min the reaction mixture was filtered and concentrated in vacuo to afford a glassy oil. This was purified by preparative HPLC (condition 8) to give a light brown oil which was partitioned between dichloromethane (15 ml) and aqueous potassium carbonate solution (7% w:v, 5 ml). The layers were separated and the organic layer was washed with water (5 ml), dried (MgSO4), filtered and concentrated in vacuo to afford the title compound as a colourless oil (69 mg, 50%).

Workup

  1. customThe rapidly stirred reaction mixture
  2. filtrationAfter 30 min the reaction mixture was filtered
  3. concentrationconcentrated in vacuo
  4. customto afford a glassy oil
  5. customThis was purified by preparative HPLC (condition 8)
  6. customto give a light brown oil which
  7. customwas partitioned between dichloromethane (15 ml) and aqueous potassium carbonate solution (7% w:v, 5 ml)
  8. customThe layers were separated
  9. washthe organic layer was washed with water (5 ml)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c2e138fd145d49a6887abb84da7016f8
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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