Oxygen → 5,11-Dihydro-11-ethyl-2-fluoro-8-(2-hydroxyethyl)-5-methyl-6H-dipyrido [3,2-b:2',3'-e][1,4]diazepin-6-one

HRID 2229319Notes

Reaction equation

HRID 2229319 reaction equation
[O:1]=O.[CH2:3]([N:5]1[C:11]2[N:12]=[CH:13][C:14]([CH2:16][CH:17]=C)=[CH:15][C:10]=2[C:9](=[O:19])[N:8]([CH3:20])[C:7]2[CH:21]=[CH:22][C:23]([F:25])=[N:24][C:6]1=2)[CH3:4].[BH4-].[Na+].[NH4+].[Cl-]>C(Cl)Cl.CO>[CH2:3]([N:5]1[C:11]2[N:12]=[CH:13][C:14]([CH2:16][CH2:17][OH:1])=[CH:15][C:10]=2[C:9](=[O:19])[N:8]([CH3:20])[C:7]2[CH:21]=[CH:22][C:23]([F:25])=[N:24][C:6]1=2)[CH3:4]

Participants

7

Reactant 4

HCID 977OxygenHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydride2×HCID 18753043HCID 18753043, compound

Product 1

HCID 112670525,11-Dihydro-11-ethyl-2-fluoro-8-(2-hydroxyethyl)-5-methyl-6H-dipyrido [3,2-b:2',3'-e][1,4]diazepin-6-oneYield 72%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A stream of ozonised oxygen was bubbled through a cold (−78° C.) solution of 5,11-dihydro-11-ethyl-2-fluoro-5-methyl-8-(2-propenyl)-6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one (22.38 g, 71.6 mmol) in CH2Cl2 (100 mL) and MeOH (100 mL) for 3 h. A stream of N2 was next bubbled through the solution for 15 min and then solid NaBH4 (5.05 g, 133 mmol) was added to the solution. The reaction mixture was allowed to warm to room temperature. After 1 h, an additional portion of NaBH4 (1.62 g, 43.0 mmol) was added to the reaction mixture. After an additional hour, aqueous saturated NH4Cl (150 mL) was added and the mixture was stirred at room temperature for 30 min. The organic solvents were removed under reduced pressure. Water (200 mL) was added and the mixture was extracted with CHCl3 (3×300 mL). The combined organic layers were dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (EtOAc:CHCl3, 4:1) to give the title compound (19.7 g, 72% yield) as a white solid.

Workup

  1. customA stream of N2 was next bubbled through the solution for 15 min
  2. waitAfter an additional hour
  3. customThe organic solvents were removed under reduced pressure
  4. additionWater (200 mL) was added
  5. extractionthe mixture was extracted with CHCl3 (3×300 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography (EtOAc:CHCl3, 4:1)

Sources & evidence

ORD record
ord-6e131e850c9b4753992e11fa0d5b1bc5
Source dataset
uspto-grants-2002_07
Patent number
US06420359B1

Reaction notes

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