Reaction #12019

Reaction equation

water

ethyl acetate

(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

intermediate b

(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

triethylamine

→

product

Yield 74.4%

(4R,9aR)-4-Methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2,6-dicarboxylic acid 2-tert-butyl ester 6-methyl ester

Yield 74.4%

Solvents

brine

methanol

Conditions

Workup

1. 1
   Extractionwas extracted with further portions of ethyl acetate
2. 2
   OtherThe combined organic layers were separated
3. 3
   Dryingdried over magnesium sulfate
4. 4
   Filtrationfiltered
5. 5
   OtherThe residue was purified by chromatography on silica gel (0.032–0.063 mm)

Procedure

To a solution of 6.0 g (16.3 mmol) (4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (Example 5, intermediate b) in 60 ml methanol were added 0.57 g (0.8 mmol) and 3.4 ml (2.5 g, 24.4 mmol) triethylamine and the reaction mixture was stirred at 80 deg C. for 24 h under a carbon monoxide atmosphere of 40 bar. The suspension was cooled to room temperature, poured into a mixture of water, ethyl acetate and brine and was extracted with further portions of ethyl acetate. The combined organic layers were separated, dried over magnesium sulfate and filtered. The residue was purified by chromatography on silica gel (0.032–0.063 mm) to afford the product as a light yellow foam (74.4%).

Source