Reacción #944247

Ecuación de reacción

hydrogen

3-cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl ester

p-toluenesulfonic acid monohydrate

→

title compound

Rendimiento 89.0%

3-Aminomethyl-indan-1-carboxylic acid methyl ester

Rendimiento 89.0%

Disolventes

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   FiltraciónAfter this time, the reaction mixture was filtered through Celite and typically used filtrate in the next step (Example 60D)
2. 2
   Concentraciónthe filtrate was concentrated in vacuo
3. 3
   Otrothe residue was partitioned between 30 mL of methylene chloride and 20 mL of a saturated aqueous solution of sodium carbonate
4. 4
   Extracciónthe aqueous layer was extracted with 15 mL of methylene chloride
5. 5
   Lavadothe combined aqueous layers were washed with 40 mL of a saturated aqueous solution of sodium chloride
6. 6
   Secadothe organic solution was dried over anhydrous sodium sulfate
7. 7
   Concentraciónconcentrated

Procedimiento

To a solution of 5.79 g of 3-cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl ester (20.0 mmol, 1.0 equivalent) in 25 mL of methanol was added 5.71 g of p-toluenesulfonic acid monohydrate (30.0 mmol, 1.5 equivalent). The solution was stirred for 15 minutes and then 4.21 g of 20% palladium hydroxide on carbon, 50% wet by weight, (3.00 mmol, 0.15 equivalent) was added. The reaction mixture was subjected to hydrogenolysis at 50 psi of hydrogen over 24 hours. After this time, the reaction mixture was filtered through Celite and typically used filtrate in the next step (Example 60D). The isolation of the title compound was conducted as follows: the filtrate was concentrated in vacuo; the residue was partitioned between 30 mL of methylene chloride and 20 mL of a saturated aqueous solution of sodium carbonate; the aqueous layer was extracted with 15 mL of methylene chloride; the combined aqueous layers were washed with 40 mL of a saturated aqueous solution of sodium chloride; the organic solution was dried over anhydrous sodium sulfate and concentrated to afford the title compound as an oil (3.65 g, 89%) with approximately a 10:1 ratio of diastereomers; (major diastereomer) 1H NMR (400 MHz, CDCl3): δ 7.43 (dd, J=6.9, 1.6 Hz, 1H), 7.29–7.25 (m, 3H), 4.09 (t, J=8.1 Hz, 1H), 3.80 (s, 3H), 3.31–3.24 (m, 1H), 3.14 (dd, J=12.8, 4.7 Hz, 1H), 2.98 (dd, J=12.8, 7.3 Hz, 1H), 2.62–2.52 (m, 1H), 2.31–2.42 (m, 1H), 1.3 (bs, 2H).

Fuente