1-bromo-4-propan-2-ylbenzene

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: By carrying out the reaction as in Stage A of Example 1, but from 6 g of methyl (3aRS,4SR,7aRS)-2-benzyl-7-oxo-4-phenyloctahydroisoindole-3a-carboxylate in 60 cm3 of dry diethyl ether and from a solution of 4-isopropylphenyl magnesium bromide, prepared at the time of use from 4 g of 4-bromoisopropylbenzene and 0.52 g of magnesium turnings in 7 cm3 of dry diethyl ether, for eighteen hours at room temperature, 3.3 g (41%) of methyl (3aRS,4SR,7RS,7aRS)-2-benzyl-7-(4-isopropylphenyl)-7-hydroxy-4-phenyloctahydroisoindole-3a-carboxylate were obtained, after purification by flash chromatography on silica gel (230-400 mesh), elution being carried out with a gradient of mixtures of cyclohexane and of ethyl acetate (from 98/2 to 80/20 by volume), in the form of a yellow oil, the characteristic of which was as follows: the reaction as in Stage A of Example 1

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-isopropylphenylmagnesium bromide prepared from 2.35 g (96.5 mmol) magnesium and 18.15 g (96.5 mmol) 1-bromo-4-isopropylbenzene in 80 ml THF is added slowly at −78° C. to a solution of 20 g (96.5 mmol) 5-allyloxy-2-nitro-benzaldehyde in 200 ml THF. After allowing the reaction mixture to warm up to r.t. saturated aqueous ammonium chloride solution is added. Extraction with ethyl acetate followed by chromatographic purification on silica (hexane/ethyl acetate) yields (5-allyloxy-2-nitro-phenyl)-(4-isopropyl-phenyl)-methanol. is added Extraction with ethyl acetate followed by chromatographic purification on silica (hexane/ethyl acetate)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To fuming nitric acid (5 mL) cooled to 5° was added neat 4-bromoisopropylbenzene (1.0 g, 5.023 mmol) dropwise at such a rate that the reaction temperature remained below 10°. The reaction was stirred for 2 hours at 5-10°, quenched with ice (50 g), extracted with ethyl acetate (50 mL), and the organic extract was washed with water (2×25 mL) and brine (25 mL), then dried over magnesium sulfate.filtered and concentrated by rotary evaporation. The residue was purified by silica gel flash chromatography eluting with 5:95 ethyl acetate/hexanes to afford the title compound as a light yellow solid (1.03 g, 4.22 mmol, 84%). 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 1.27 (d, J=6.99 Hz, 6 H) 2.75-3.23 (m, 1 H) 7.29 (dd, J=8.82, 2.21 Hz, 1 H) 7.63 (d, J=8.09 Hz, 1 H) 7.69 (d, J=2.21 Hz, 1 H); MS (DCI) m/z 261/263 (M+NH4)+. remained below 10° quenched with ice (50 g) extracted with ethyl acetate (50 mL) the organic extract was washed with water (2×25 mL) and brine (25 mL) dried over magnesium sulfate filtered concentrated by rotary evaporation The residue was purified by silica gel flash chromatography eluting with 5:95 ethyl acetate/hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: By carrying out the reaction as in Stage A of Example 1, but from 6 g of methyl(3aRS,4SR,7aRS)-2-benzyl-7-oxo-4-phenyloctahydroisoindole-3a-carboxylate in 60 cm3 of dry diethyl ether and from a solution of 4-isopropylphenylmagnesium bromide, prepared at the time of use from 4 g of 4-bromoisopropylbenzene and 0.52 g of magnesium turnings in 7 cm3 of dry diethyl ether, for eighteen hours at room temperature, 3.3 g (41%) of methyl(3aRS,4SR,7RS,7aRS)-2-benzyl-7-(4-isopropylphenyl)-7-hydroxy-4-phenyloctahydroisoindole-3a-carboxylate were obtained, after purification by flash chromatography on silica gel (230-400 mesh), elution being carried out with a gradient of mixtures of cyclohexane and of ethyl acetate (from 98/2 to 80/20 by volume), in the form of a yellow oil, the characteristic of which was as follows: the reaction as in Stage A of Example 1

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: By carrying out the reaction as in Stage A of Example 1, but from 6 g of methyl(3aRS,4SR,7aRS)-2-benzyl-7-oxo-4-phenyloctahydroisoindole-3a-carboxylate in 60 cm3 of dry diethyl ether and from a solution of 4-isopropylphenylmagnesium bromide, prepared at the time of use from 4 g of 4-bromoisopropylbenzene and 0.52 g of magnesium turnings in 7 cm3 of dry diethyl ether, for eighteen hours at room temperature, 3.3 g (41%) of methyl(3aRS,4SR,7RS,7aRS)-2-benzyl-7-(4-isopropylphenyl)-7-hydroxy-4-phenyloctahydroisoindole-3a-carboxylate were obtained, after purification by flash chromatography on silica gel (230-400 mesh), elution being carried out with a gradient of mixtures of cyclohexane and of ethyl acetate (from 98/2 to 80/20 by volume), in the form of a yellow oil, the characteristic of which was as follows: the reaction as in Stage A of Example 1

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 128.8 g (0.8 mol) of 1H-indole-2-carboxylic acid, of 159.2 g (0.8 mol) of 4-bromocumene, of 111.6 g (0.808 mol) of potassium carbonate and of 8 g (0.1 mol) of copper oxide in 200 ml of dimethylformamide is stirred at reflux for 24 hours. After cooling, 6 l of water are added to the beige suspension obtained. The suspension is filtered and then the insoluble material is taken up in 1 l of a 5N hydrochloric acid solution. This mixture is extracted with 500 ml of dichloromethane. The organic phase is washed with water, dried over sodium sulfate and then concentrated under reduced pressure. After drying under reduced pressure, 204.4 g of a white solid are obtained, which solid is used as is in the following stage. at reflux for 24 hours After cooling obtained The suspension is filtered This mixture is extracted with 500 ml of dichloromethane The organic phase is washed with water dried over sodium sulfate concentrated under reduced pressure After drying under reduced pressure, 204.4 g of a white solid are obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-isopropylphenylmagnesium bromide prepared from 2.35 g (96.5 mmol) magnesium and 18.15 g (96.5 mmol) 1-bromo-4-isopropylbenzene in 80 ml THF is added slowly at −78° C. to a solution of 20 g (96.5 mmol) 5-allyloxy-2-nitro-benzaldehyde in 200 ml THF. After allowing the reaction mixture to warm up to r.t. saturated aqueous ammonium chloride solution is added. Extraction with ethyl acetate followed by chromatographic purification on silica (hexane/ethyl acetate) yields (5-allyloxy-2-nitro-phenyl)-(4-isopropyl-phenyl)-methanol. is added Extraction with ethyl acetate followed by chromatographic purification on silica (hexane/ethyl acetate)