Ammonium fluoride → HCID 11997224, compound

HRID 1985708Notes

Reaction equation

HRID 1985708 reaction equation
C(OC([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH:22](C(C)(C)C(C)C)O[SiH](C)C)=[C:14]([CH:33]=[O:34])[CH:13]=3)[CH2:9]1)=O)(C)(C)C.[F-].[NH4+]>CO>[NH3:8].[CH3:21][C@@H:19]1[CH2:20][NH:8][CH2:9][C@@H:10]2[N:18]1[C:17]1[N:16]=[C:15]3[CH2:22][O:34][CH2:33][C:14]3=[CH:13][C:12]=1[CH2:11]2

Participants

5

Reactant 2

HCID 25516Ammonium fluorideHCID 131727477HCID 131727477, compound

Product 2

HCID 222AmmoniaYield 25%HCID 11997224HCID 11997224, compoundYield 152.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 22.7g (0.046 mol) (4R,9aR)-6-[dimethyl-(1,1,2-trimethyl-propyl)-silanyloxymethyl]-7-formyl-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester and 22.7 g ammonium fluoride (0.61 mol) in 500 ml methanol was heated to reflux for 1 h. The reaction mixture cooled to room temperature and partitioned between water and ethyl acetate. The phases were separated and the organic phase was washed with water and brine dried over sodium sulfate filtered and evaporated. The residue was taken up in 230 ml of dichloromethane and cooled to 0° C. To the resulting solution was added 23 ml triethylsilane and 113 ml trifluoroacetic acid and the mixture was stirred with thawing to room temperature for 17 h. The resulting orange red solution was evaporated under aspirator vacuum. The residue was partitioned between 200 ml water and 200 ml ethyl acetate. The phases were separated and the organic phase was extracted twice with 100 ml water. The combined aqueous phases were mixed with 300 ml dichloromethane and the pH of the mixture was adjusted to 12.00 by addition of a 28% solution of sodium hydroxide in water. The phases were separated and the aqueous phase was extracted two more times with 100 ml dichloromethane. The combined dichloromethane phases were dried over sodium sulfate evaporated to dryness and purified by chromatography on silica gel with dichloromethane:methanol:25% aqueous ammonia=90:10:1 to yield 8.11 g (76%) of (5R,8aR)-5-methyl-1,3,5,6,7,8,8a,9-octahydro-2-oxa-4,4b,7-triaza-cyclopenta[b]fluorene as yellow orange foam. (MS: 232 (M+H+))

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 1 h
  3. custompartitioned between water and ethyl acetate
  4. customThe phases were separated
  5. washthe organic phase was washed with water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. temperaturecooled to 0° C
  10. additionTo the resulting solution was added 23 ml triethylsilane and 113 ml trifluoroacetic acid
  11. customThe resulting orange red solution was evaporated under aspirator vacuum
  12. customThe residue was partitioned between 200 ml water and 200 ml ethyl acetate
  13. customThe phases were separated
  14. extractionthe organic phase was extracted twice with 100 ml water
  15. additionThe combined aqueous phases were mixed with 300 ml dichloromethane
  16. additionthe pH of the mixture was adjusted to 12.00 by addition of a 28% solution of sodium hydroxide in water
  17. customThe phases were separated
  18. extractionthe aqueous phase was extracted two more times with 100 ml dichloromethane
  19. dry with materialThe combined dichloromethane phases were dried over sodium sulfate
  20. customevaporated to dryness
  21. custompurified by chromatography on silica gel with dichloromethane

Sources & evidence

ORD record
ord-d61a0f0d03734815b29914982e6ba653
Source dataset
uspto-grants-2009_06
Patent number
US07547699B2

Reaction notes

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