2,2-dimethyl-3H-1-benzofuran

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:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,3-dihydro-2,2-dimethylbenzofuran (25 g) and tetramethylethylenediamine (46 g) in heptane (250 ml) was treated dropwise at room temperature with 1.6 M BuLi in hexane (250 ml). After stirring for 1.5 h at 30-40° C. the mixture was cooled to -40° C. and 1-benzyl-4-piperidinone (32 g) was added dropwise at -40° C. The reaction mixture was allowed to warm to room temperature during 3 h followed by quench with water. After concentrating the reaction mixture in vacuo dichloromethane (500 ml) was added followed by wash with water (3×500 ml). Removal of solvent in vacuo gave an oil which was purified by flash chromatography (silica gel, heptane/ethyl acetate/triethylamine 50:48:2) giving an oil. Addition of heptane gave the product, 7-(1-benzyl-4-hydroxy-4-piperidinyl)-2,3-dihydro-2,2-dimethylbenzofuran as a solid (11 g). was cooled to -40° C. to warm to room temperature during 3 h by quench with water After concentrating the reaction mixture in vacuo dichloromethane (500 ml) was added by wash with water (3×500 ml) Removal of solvent in vacuo gave an oil which was purified by flash chromatography (silica gel, heptane/ethyl acetate/triethylamine 50:48:2) giving an oil

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

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

Procedure: Using 2,2-dimethyl-2,3-dihydro-1-benzofuran (3.0 g) and 5-chlorovaleryl chloride (3.4 g) according to the same method as that of Reference Example 1, the title compound was obtained as a fine yellow oil (3.6 g).

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

Procedure: Using 2,2-dimethyl-2,3-dihydro-1-benzofuran (3.0 g) and 5-chlorovaleryl chloride (3.4 g) according to the same method as that of Reference Example 1, the title compound was obtained as a fine yellow oil (3.6 g).

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

Procedure: 2,2-Dimethyl-2,3-dihydrobenzo[b]furan (prepared according to the method of Baker and Shulgin, J. Org. Chem., 28, 1963, 2468) (500 mg, 3.38 mmol) was taken up in dichloroethane (5.5 ml) and stirred at room temperature under nitrogen, and N-bromosuccinimide (661 mg, 3.72 mmol) added in one portion. The reaction was then refluxed for 2 h, ether was added (10 ml) and a white precipitate of succinimide filtered off. The filtrate was evaporated to dryness, and then purified by column chromatography using 5% ether in pentane as eluant to give the title product (604 mg, 79%); 1HNMR (400 MHz, CDCl3) δ: 1.43 (s, 6H), 2.92 (s, 2H), 6.54 (d, 1H), 7.16 (d, 1H), 7.19 (s, 1H); LRMS: M+H, 227. (TS+). The reaction was then refluxed for 2 h a white precipitate of succinimide filtered off The filtrate was evaporated to dryness purified by column chromatography

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,3-dihydro-2,2-dimethylbenzofuran (25 g) and tetramethylethylenediamine (46 g) in heptane (250 ml) was treated dropwise at room temperature with 1.6 M BuLi in hexane (250 ml). After stirring for 1.5 h at 30-40° C. the mixture was cooled to -40° C. and 1-benzyl-4-piperidinone (32 g) was added dropwise at -40° C. The reaction mixture was allowed to warm to room temperature during 3 h followed by quench with water. After concentrating the reaction mixture in vacuo dichloromethane (500 ml) was added followed by wash with water (3×500 ml). Removal of solvent in vacuo gave an oil which was purified by flash chromatography (silica gel, heptane/ethyl acetate/triethylamine 50:48:2) giving an oil. Addition of heptane gave the product, 7-(1-benzyl-4-hydroxy-4-piperidinyl)-2,3-dihydro-2,2-dimethylbenzofuran as a solid (11 g). was cooled to -40° C. to warm to room temperature during 3 h by quench with water After concentrating the reaction mixture in vacuo dichloromethane (500 ml) was added by wash with water (3×500 ml) Removal of solvent in vacuo gave an oil which was purified by flash chromatography (silica gel, heptane/ethyl acetate/triethylamine 50:48:2) giving an oil

Conditions: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,3-dihydro-2,2-dimethylbenzofuran (25 g) and tetramethylethylenediamine (46 g) in heptane (250 ml) was treated dropwise at room temperature with 1.6 M BuLi in hexane (250 ml). After stirring for 1.5 h at 30-40° C. the mixture was cooled to -40° C. and 1-benzyl-4-piperidinone (32 g) was added dropwise at -40° C. The reaction mixture was allowed to warm to room temperature during 3 h followed by quench with water. After concentrating the reaction mixture in vacuo dichloromethane (500 ml) was added followed by wash with water (3×500 ml). Removal of solvent in vacuo gave an oil which was purified by flash chromatography (silica gel, heptane/ethyl acetate/triethylamine 50:48:2) giving an oil. Addition of heptane gave the product, 7-(1-benzyl-4-hydroxy-4-piperidinyl)-2,3-dihydro-2,2-dimethylbenzofuran as a solid (11 g). was cooled to -40° C. to warm to room temperature during 3 h by quench with water After concentrating the reaction mixture in vacuo dichloromethane (500 ml) was added by wash with water (3×500 ml) Removal of solvent in vacuo gave an oil which was purified by flash chromatography (silica gel, heptane/ethyl acetate/triethylamine 50:48:2) giving an oil

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: During a one hour period an ice cold mixture of 43 mL concentrated nitric acid and 50 mL of concentrated sulfuric acid was added dropwise to 100.0 g (0.67 mole) 2,3-dihydro-2,2-dimethylbenzofuran while maintaining the temperature of 5° C. After complete addition the mixture was stirred at 0° C. for 2.5 hours. The reaction mixture was poured into ice water and the total extracted with diethyl ether. The extract was dried over anhydrous magnesium chloride and filtered. Evaporation of the filtrate under reduced pressure produced a black oil. Purification of this oil by column chromatography on silica gel eluting with toluenen-hexane (9:1), yielded 50.0 g of 2,3-dihydro-2,2-dimethyl-5-nitrobenzofuran as a solid. After complete addition the mixture the total extracted with diethyl ether The extract was dried over anhydrous magnesium chloride filtered Evaporation of the filtrate under reduced pressure produced a black oil Purification of this oil by column chromatography on silica gel eluting with toluenen-hexane (9:1)

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

Procedure: 2,2-Dimethyl-2,3-dihydrobenzo[b]furan (prepared according to the method of Baker and Shulgin, J. Org. Chem., 28, 1963, 2468) (500 mg, 3.38 mmol) was taken up in dichloroethane (5.5 ml) and stirred at room temperature under nitrogen, and N-bromosuccinimide (661 mg, 3.72 mmol) added in one portion. The reaction was then refluxed for 2 h, ether was added (10 ml) and a white precipitate of succinimide filtered off. The filtrate was evaporated to dryness, and then purified by column chromatography using 5% ether in pentane as eluant to give the title product (604 mg, 79%); 1HNMR (400 MHz, CDCl3) δ: 1.43 (s, 6H), 2.92 (s, 2H), 6.54 (d, 1H), 7.16 (d, 1H), 7.19 (s, 1H); LRMS: M+H, 227. (TS+). The reaction was then refluxed for 2 h a white precipitate of succinimide filtered off The filtrate was evaporated to dryness purified by column chromatography