Reaction #715895

Reaction equation

(2-benzyloxy-ethyl)-phenyl-amine

(2-Benzyloxy-ethyl)-phenyl-amine

3-bromo-2-hydroxy-cyclohex-1-enecarboxylic acid ethyl ester

3-Bromo-2-hydroxy-cyclohex-1-enecarboxylic acid ethyl ester

→

9-(2-benzyloxy-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid ethyl ester

Yield 72.0%

9-(2-Benzyloxy-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid ethyl ester

Yield 72.0%

Solvents

propan-2-ol

Conditions

Workup

1. 1
   TemperatureThe mixture was heated
2. 2
   Temperatureto reflux under N2 for 16 h
3. 3
   Concentrationconcentrated in vacuo
4. 4
   workup.DISSOLUTIONThe residue was dissolved in ethyl acetate (300 mL)
5. 5
   Washwashed with 2 N HCl (100 mL), water (2×100 mL) and aqueous potassium carbonate solution (2×100 mL)
6. 6
   Otherthen dried
7. 7
   Concentrationconcentrated in vacuo
8. 8
   OtherThe crude material was purified by silica gel chromatography
9. 9
   Washeluting with petrol (A) and ethyl acetate (B) (2.5-40% B, 17 CV, 330 g, 100 mL/min)

Procedure

A mixture of (2-benzyloxy-ethyl)-phenyl-amine (21; prepared according to Example 3(c)) (8.0 g, 26 mmol) and 3-bromo-2-hydroxy-cyclohex-1-enecarboxylic acid ethyl ester (4; prepared according to Example 1(d)) (3.2 g, 13 mmol) was stirred under N2 at 50° C. for 3 h and the reaction turned brown. The resulting mixture was dissolved in propan-2-ol (30 mL) and dry zinc chloride (10.6 g, 78 mmol) was added. The mixture was heated to reflux under N2 for 16 h and then concentrated in vacuo. The residue was dissolved in ethyl acetate (300 mL) and washed with 2 N HCl (100 mL), water (2×100 mL) and aqueous potassium carbonate solution (2×100 mL) then dried and concentrated in vacuo. The crude material was purified by silica gel chromatography eluting with petrol (A) and ethyl acetate (B) (2.5-40% B, 17 CV, 330 g, 100 mL/min) to give 3.49 g (72%) of 9-(2-benzyloxy-ethyl)-2,3,4,9-tetrahydro-1H-carbazole-4-carboxylic acid ethyl ester (25) as an oil. The structure was confirmed by 13C NMR (75 MHz, CDCl3) δC 14.2, 20.5, 21.8, 26.5, 38.6, 42.9, 60.4, 68.7, 73.2, 106.4, 108.8, 118.7, 120.7, 127.4, 127.5, 128.3, 136.2, 136.9, 137.8, 175.0.

Source