Aluminium lithium hydride → 8-Fluoro-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

HRID 2246997Notes

Reaction equation

HRID 2246997 reaction equation
[F:1][C:2]1[CH:14]=[CH:13][C:5]2[C:6](=O)[NH:7][CH2:8][C:9](=O)[NH:10][C:4]=2[CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[F:1][C:2]1[CH:14]=[CH:13][C:5]2[CH2:6][NH:7][CH2:8][CH2:9][NH:10][C:4]=2[CH:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 21904832HCID 21904832, compound

Product 1

HCID 219048308-Fluoro-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

THF (19.1 mL) was added to a flask containing 8-fluoro-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione (2.11 g, 10.9 mmol). Dropwise over 10 minutes was added lithium aluminum hydride in 1M THF (48.9 mL, 48.9 mmol). The reaction mixture was heated to reflux for 5.5 hours, and then let cool to room temperature overnight. After 18 hours, no starting material was seen. The reaction was quenched with water, 15% sodium hydroxide and another portion of water. After the white precipitate was filtered off, THF was removed from the filtrate. The contents of the flask were then transferred to a separatory funnel using ethyl acetate and water, and extracted with ethyl acetate (3×). The combined organic extracts were washed with brine (1×) and then dried with magnesium sulfate, filtered and concentrated to give a yellow oil. Further purification (15% ammonia 2M solution in ethanol/ethyl acetate) yielded the desired compound.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 5.5 hours
  3. customThe reaction was quenched with water, 15% sodium hydroxide
  4. filtrationAfter the white precipitate was filtered off
  5. customTHF was removed from the filtrate
  6. customThe contents of the flask were then transferred to a separatory funnel
  7. extractionextracted with ethyl acetate (3×)
  8. washThe combined organic extracts were washed with brine (1×)
  9. dry with materialdried with magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto give a yellow oil
  13. customFurther purification (15% ammonia 2M solution in ethanol/ethyl acetate)

Sources & evidence

ORD record
ord-ca6f71c5d09a4abda65c89151fc85eac
Source dataset
uspto-grants-2010_03
Patent number
US07687620B2

Reaction notes

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