Reaction #12042

Reaction equation

ammonium chloride

tert-butyllithium

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

acetaldehyde

→

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

Solvents

diethyl ether

Conditions

Workup

1. 1
   TemperatureAfter warming to −75 deg C
2. 2
   Extractionextracted three times with ethyl acetate
3. 3
   WashThe combined organic layers were washed with brine
4. 4
   Dryingdried over magnesium sulfate
5. 5
   Filtrationfiltered
6. 6
   Otherevaporated
7. 7
   OtherThe residue was chromatographed on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (2:3) as eluant
8. 8
   Otherto afford a first batch of compound
9. 9
   workup.ADDITIONThe remaining product-containing fractions
10. 10
    Otherchromatographed again
11. 11
    Otherto yield a second batch of compound (56.9% total)

Procedure

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 in 250 ml diethyl ether was cooled to −100 deg C. and treated with 11.9 ml (17.9 mmol) tert-butyllithium (1.5 M in n-pentane). After 15 min, 1.0 ml (0.79 g, 17.9 mmol) acetaldehyde was added and the reaction was stirred for 40 min at the same temperature. After warming to −75 deg C. the reaction mixture was poured onto 10% aqueous ammonium chloride solution and extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was chromatographed on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (2:3) as eluant to afford a first batch of compound. The remaining product-containing fractions were pooled and chromatographed again to yield a second batch of compound (56.9% total).

Source