HCID 69358276, compound → HCID 69358754, compound

HRID 1272169Notes

Reaction equation

HRID 1272169 reaction equation
[C:1]([O:5][C:6](=[O:23])[NH:7][CH2:8][C@H:9]([N:11]1[C:15]2=[N:16][CH:17]=[C:18]([F:20])[CH:19]=[C:14]2[CH:13]=[C:12]1[CH2:21]O)[CH3:10])([CH3:4])([CH3:3])[CH3:2]>ClCCl.[O-2].[O-2].[Mn+4]>[C:1]([O:5][C:6]([N:7]1[CH2:8][C@@H:9]([CH3:10])[N:11]2[C:12](=[CH:13][C:14]3[C:15]2=[N:16][CH:17]=[C:18]([F:20])[CH:19]=3)[CH2:21]1)=[O:23])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 1

HCID 69358276HCID 69358276, compound

Product 1

HCID 69358754HCID 69358754, compoundYield 74.5%

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of 5.4 g (R)-[2-(5-fluoro-2-hydroxymethyl-pyrrolo[2,3-b]pyridin-1-yl)-propyl]-carbamic acid tert-butyl ester in 55 mL dichloromethane was added 7.40 g manganese dioxide and the mixture was stirred at room temperature for 1 h. Another 7.40 g manganese dioxide was added and the mixture was stirred at room temperature for 4 h. The solids were removed by filtration over dicalite. The mother liquor was evaporated and the residue was taken up in 50 mL dichloromethane and 3.0 mL acetic acid and 10.62 g sodium triacetoxyborohydride was added. An instantaneous gas evolution took place and the mixture warmed up to ca 35° C. The mixture was stirred at ambient temperature for 18 h. To the reaction mixture was added 50 mL water. A marked gas evolution took place. The mixture was stirred at room temperature for 15 min. The phases were separated and the organic phase was evaporated to dryness and purified by chromatography on silica gel with heptane:ethyl acetate=1:1 as eluent to yield a slightly yellow oil which crystallized on standing to yield 3.80 g (R)-7-fluoro-4-methyl-3,4-dihydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester as slightly yellow crystals; m.p.: 85–87° C.

Workup

  1. stirringthe mixture was stirred at room temperature for 4 h
  2. customThe solids were removed by filtration over dicalite
  3. customThe mother liquor was evaporated
  4. addition3.0 mL acetic acid and 10.62 g sodium triacetoxyborohydride was added
  5. temperaturethe mixture warmed up to ca 35° C
  6. stirringThe mixture was stirred at ambient temperature for 18 h
  7. additionTo the reaction mixture was added 50 mL water
  8. stirringThe mixture was stirred at room temperature for 15 min
  9. customThe phases were separated
  10. customthe organic phase was evaporated to dryness
  11. custompurified by chromatography on silica gel with heptane
  12. customethyl acetate=1:1 as eluent to yield a slightly yellow oil which
  13. customcrystallized

Sources & evidence

ORD record
ord-9bec86af0b664a9992db8e0be6531249
Source dataset
uspto-grants-2007_04
Patent number
US07208494B2

Reaction notes

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