Réaction #71255

Équation de réaction

sodium hydroxide

4-hydroxy-4-phenylethynyl-octahydro-indole-1-carboxylic acid ethyl ester

triethylamine

phosphorous oxychloride

citric acid

→

(±)-(RS)-4-phenylethynyl-2,3,5,6,7,7a-hexahydro-indole-1-carboxylic acid ethyl ester

Rendement 1.1%

Conditions de réaction

Traitement

1. 1
   ExtractionThe mixture is extracted with dichloromethane
2. 2
   Lavagethe organic extracts are washed with brine
3. 3
   Séchagedried over anhydrous magnesium sulfate
4. 4
   Autreevaporated in vacuo
5. 5
   AutreThe residue is chromatographed on silica with hexane and diethyl ether (4:1 v/v)
6. 6
   workup.ADDITIONThe first product containing fractions

Mode opératoire

A solution of 4-hydroxy-4-phenylethynyl-octahydro-indole-1-carboxylic acid ethyl ester (1.0 g, 3.19 mmol), triethylamine (2.2 ml, 16 mmol) and phosphorous oxychloride 0.877 ml, 10 mmol) is heated to 40° C. for 4 hours. The dark mixture is cooled to 0° C. and treated with 1M sodium hydroxide (5 ml) and then acidified with a 10% aqueous citric acid solution. The mixture is extracted with dichloromethane, the organic extracts are washed with brine, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue is chromatographed on silica with hexane and diethyl ether (4:1 v/v). The first product containing fractions afforded (±)-(RS)-4-phenylethynyl-2,3,5,6,7,7a-hexahydro-indole-1-carboxylic acid ethyl ester (10 mg, 1%) as a yellowish oil. 1H-NMR (400 MHz; CDCl3): 7.44 (m, 2H), 7.32 (m, 3H), 4.24-3.97 (m, 3H), 3.8 (m, 1H), 3.25 (m, 1H), 2.93 (m, 1H), 2.56 (m, 1H), 2.28 (m, 2H), 1.90 (m, 1H), 1.60 (m, 2H), 1.28 (t, J=7 Hz, 3H), 1.14 (m, 1H). ES-MS (+): 296.1. After collecting a mixture of the two products (475 mg, 50%), the third product containing fractions yielded (±)-(3RS,7aRS)-4-phenylethynyl-2,3,3a,6,7,7a-hexahydro-indole-1-carboxylic acid ethyl ester (64 mg, 7%) as a yellowish oil. 1H-NMR (400 MHz; CDCl3): 7.43 (m, 2H), 7.31 (m, 3H), 6.27 (m, 1H), 4.15 (m, 2H), 4.01-3.83 (m, 1H), 3.46 (m, 2H), 2.82 (m, 1H), 2.37-1.82 (m, 5H), 1.57 (m, 1H), 1.27 (t, J=7 Hz, 3H). ES-MS (+): 296.2.

Source