Org Prep Daily

September 20, 2009

4,5,6,7-tetrahydroindole-2-carboxaldehyde

Filed under: procedures — milkshake @ 5:38 pm

tetrahydroindole

4-oxo-4,5,6,7-tetrahydroindole 5.15g (38.1 mmol; TCI-US) solution in anh THF 0.45L in a 1L flask was placed on ambient water bath and solid LAH 4.0g was added carefully, portion-wise, into the stirred solution, (4×0.5g then 2x1g – very exothermic, gas evolution!). The mixture was then placed on oil bath and refluxed under Ar on a 75-80C oil bath for 26 hours. The reaction mixture was cooled on ambient water bath, quenched by sequential addition of ethyl acetate 4mL followed by dropwise water addition, 4mL (very slowly – gas evolution), followed by 15% wt NaOH solution 12mL followed by additional water 4mL. The resulting slurry was stirred vigorously for 30 min, the salts were removed by filtration (the cake was washed thoroughly with THF) and the filtrates were concentrated on rotovap. The oily residue was distilled on highvac using a short-path distillation apparatus. (The material distilled pure; no fractionation was necessary, bp 57-60C/0.7 Torr).

Y=3.83g (84%th) of tetrahydroindole as an oily colorless liquid that gradually turns yellowish on light and air.[Note 1]

Anhydrous DMF 20mL in a 250mL flask was cooled on ice bath and neat POCl3 4.6mL (50mmol) was added dropwise (exothermic) under Ar. After 10 min, a solution of tetrahydroindole 3.83g (32.14mmol) in anh DMF 10mL was gradually added over 10min (exothermic) followed by additional anh DMF 2x5mL to wash the flask and the syringe. The cooling bath was replaced with ambient water bath and the reaction was stirred at RT under Ar for 13 hours (overnight). The reaction was quenched by addition of water 20mL followed by 15% wt NaOH solution 40mL. After 10 min, additional 15% NaOH 25mL was added. followed by water 100mL and the mixture was stirred vigorously for 30min on ambient water bath. The precipitated product was collected by filtration, compressed on the Buchner funnel, washed thoroughly with water, dried by suction and on highvac. Y= 4.282g (90.5%) of light tan shiny flakes

1H(d6-DMSO, 400MHz): 11.609(br s, 1H), 9.268(s, 1H), 6.679(s, 1H), 2.557(t, 5.9Hz, 2H), 2.446(t, 5.9Hz, 2H), 1.693(m, 4H)

Note 1: Tetrahydroindole is commercially available but is rather expensive. It has a strong unpleasant indole-like fecal odor – do not spill it outside the hood. Because of the oxidation-related darkening, it is best used within few days.

The Shocking Blue Green Theme. Blog at WordPress.com.

Follow

Get every new post delivered to your Inbox.

Join 139 other followers