Hydrogen Peroxide → 2-chloro-5,11-dihydro-11-ethyl-8-(beta-hydroxy)ethyl-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one

HRID 724967Notes

Reaction equation

HRID 724967 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[C:8]3[CH:18]=[C:17]([CH:19]=[CH2:20])[CH:16]=[N:15][C:9]=3[N:10]([CH2:13][CH3:14])[C:11]=2[N:12]=1.B.[O:24]1CCCC1.[OH-].[Na+].OO>O.O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[C:8]3[CH:18]=[C:17]([CH2:19][CH2:20][OH:24])[CH:16]=[N:15][C:9]=3[N:10]([CH2:13][CH3:14])[C:11]=2[N:12]=1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 197111422-chloro-5,11-dihydro-11-ethyl-5-methyl-8-vinyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one

Product 1

HCID 114048102-chloro-5,11-dihydro-11-ethyl-8-(beta-hydroxy)ethyl-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-oneYield 35.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

The 2-chloro-5,11-dihydro-11-ethyl-5-methyl-8-vinyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (1.40 g, 4.45 mmol) was dissolved tetrahydrofuran (20 mL) and treated with borane-tetrahydrofuran complex (1.0M in tetrahydrofuran, 8.9 mL, 8.9 mmol). After 2 hours the mixture was treated dropwise with water (5 mL). Then 15% aqueous sodium hydroxide (5 mL) and 30% aqueous hydrogen peroxide was added and the mixture was warmed to 40° C. for 2 hours. The cooled solution was extracted with dichloromethane (3×20 mL) and ethyl acetate (3×50 mL). The combined organics were washed with brine, dried over sodium sulfate, concentrated and the mixture of regioisomers were separated by flash chromatography (1:1 hexanes/ethyl acetate to ethyl acetate gradient) to give 2-chloro-5,11-dihydro-11-ethyl-8-(β-hydroxy)ethyl-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (0.52 g, 35%), m.p. 57°-59° C., and 2-chloro-5,11-dihydro-11-ethyl-8-(α-hydroxy)ethyyl-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (0.15 g, 10%), m.p. 65°-67° C.

Workup

  1. extractionThe cooled solution was extracted with dichloromethane (3×20 mL) and ethyl acetate (3×50 mL)
  2. washThe combined organics were washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. additionthe mixture of regioisomers
  6. customwere separated by flash chromatography (1:1 hexanes/ethyl acetate to ethyl acetate gradient)

Sources & evidence

ORD record
ord-b2318aa2d67a436badc0ff7954f2b0ca
Source dataset
uspto-grants-1998_01
Patent number
US05705499

Reaction notes

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