Ammonium fluoride → HCID 11997224, compound

Participants

Reaction Steps

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+))

Provenance & Evidence