Acetonitrile → 10H-pyrazolo[5,1-c][1,4]benzoxazepine-2-carbaldehyde

HRID 1744944Notes

Reaction equation

HRID 1744944 reaction equation
[H-].[Na+].[N:3]1[N:12]2[C:6]([CH2:7][O:8][C:9]3[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=3[CH2:11]2)=[CH:5][C:4]=1[CH2:17][OH:18].C[N+]1([O-])CCOCC1.C(#N)C>CN(P(N(C)C)(N(C)C)=O)C.C1(C)C=CC=CC=1.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[NH:3]1[N:12]2[C:6](=[CH:7][O:8][C:9]3[CH:16]=[CH:15][CH:14]=[CH:13][C:10]=3[CH2:11]2)[CH:5]=[C:4]1[CH:17]=[O:18]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 24758Sodium hydrideHCID 82029Methyl morpholine oxideHCID 222244534H,10H-pyrazolo[5,1-c][1,4]benzoxazepin-2-ylmethanol

Product 1

HCID 2222448910H-pyrazolo[5,1-c][1,4]benzoxazepine-2-carbaldehyde

Reagents, catalysts & solvents 3

HCID 178419074HCID 178419074, compoundCatalystHCID 1140TolueneSolventHCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
95 °C

Procedure

The diol compound (3.83 g, 16.21 mmol) in HMPA (24 ml) was added to a suspension of NaH (60%, 1.34 g, 33.5 mmol) in toluene (330 ml) under N2. Rapidly heated to 95° C. for three hours and cooled to room temperature. Quenched with water and extracted with EtOAc. Washed organics with water and brine. Dried organics over sodium sulfate and filtered and concentrated. Purified with silica gel column and 2% MeOH in CH2Cl2. Obtained 4H,10H-pyrazolo[5,1-c][1,4]benzoxazepin-2-ylmethanol (white solid). Yield: 0.71 g 20%. 4H,10H-pyrazolo[5,1-c][1,4]benzoxazepin-2-ylmethanol (0.71 g, 3.28 mmol), 4-methylmorpholine N-oxide (1/198 g, 10.23 mmol), molecular sieves (powder, 4 angstroms) (3.32 g), and acetonitrile (0.07M) were placed together under N2. Tetrapropylammoniumperruthenate (0.113 g, 0.322 mmol) was added and after three hours the reaction solution was filtered through celite and concentrated. Purified with silica gel column and 1:1 EtOAc/Hexane. Obtained 4H, 10H-pyrazolo[5,1-c][1,4]benzoxazepine-2-carbaldehyde (white solid). Yield: 0.31 g 44%.

Workup

  1. temperaturecooled to room temperature
  2. customQuenched with water
  3. extractionextracted with EtOAc
  4. filtrationDried organics over sodium sulfate and filtered
  5. concentrationconcentrated
  6. customPurified with silica gel column and 2% MeOH in CH2Cl2
  7. filtrationwas filtered through celite
  8. concentrationconcentrated
  9. customPurified with silica gel column and 1:1 EtOAc/Hexane

Sources & evidence

ORD record
ord-8c035fedc6d9495bb0e0460b15a09b68
Source dataset
uspto-grants-2006_03
Patent number
US07018997B2

Reaction notes

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