methyl 2,3-dihydro-1H-indene-2-carboxylate

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:

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolve diisopropylamine (1.90 mL, 7.8 mmol) in anhydrous tetrahydrofuran (8 mL), cool to -20° C. and place under an argon atmosphere. Add, by dropwise addition, n-butyllithium (3.12 mL of a 2.5N solution in hexanes, 7.8 mmol) and stir for 20 minuses while cooling to -70° C. Add, by dropwise addition, a solution of 2-carbomethoxy-indan (1.34 g, 7.8 mmol) in anhydrous tetrahydrofuran (8 mL). Stir at -70° C. for an additional 30 minutes then add trimethylsilyl chloride (freshly distilled from barium oxide, 1.0 mL, 7.8 mmol). Allow to warm to 10° C., evaporate the solvent in vacuo and dry the residue under vacuum for 30 minutes. Suspend the residue in methylene chloride (30 mL), add zinc bromide (300 mg, 1.3 mmol) followed by t-butyl chloromethylsulfide (1.08 g, 7.8 mmol). Stir for 15 minutes as room temperature and add additional zinc bromide (500 mg, 2.2 mmol). Pour onto excess saturated sodium hydrogen carbonate and shake vigorously. Separate the organic phase and extract the aqueous phase with methylene chloride (30 mL). Combine the organic phases, cry (MgSO4) and evaporate the solvent in vacuo to give crude product as a brown oil (2.12 g, 98%). Purify by silica gel chromatography (30°-70° C. methylene chloride/hexane) and recrystallize (methanol) to give 2-carbomethoxy-2-(t-butyl)thiomethylindan as a crystalline solid (1.3 g, 61%). while cooling to -70° C Add, by dropwise addition Stir at -70° C. for an additional 30 minutes add trimethylsilyl chloride (freshly distilled from barium oxide, 1.0 mL, 7.8 mmol) Allow to warm to 10° C. evaporate the solvent in vacuo dry the residue under vacuum for 30 minutes Stir for 15 minutes as room temperature Separate the organic phase extract the aqueous phase with methylene chloride (30 mL) Combine the organic phases, cry (MgSO4) and evaporate the solvent in vacuo to give crude product as a brown oil (2.12 g, 98%) Purify by silica gel chromatography (30°-70° C. methylene chloride/hexane) recrystallize (methanol)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Dissolve 2-carboxy-indan (2.5 g, 15.4 mmol) in methanol and cool to 0° C. Saturate with hydrochloride gas then add 2,2-dimethoxypropane (2-3 mL). Stir overnight then evaporate the solvent in vacuo. Purify by silica gel chromatography (2:1 methylene chloride/hexane) to give 2-carbomethoxy-indan as a water white oil. (2.04 g, 75%). Saturate with hydrochloride gas then evaporate the solvent in vacuo Purify by silica gel chromatography (2:1 methylene chloride/hexane)

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

Procedure: Dissolve 2-indancarboxylic acid (3.82 g, 23.5 mmol) in methanol (60 mL) and treat with dimethoxypropane (5.8 mL, 47 mmol) and sulfuric acid (0.8 mL). Stir at room temperature for 6 days. Evaporate the solvent in vacuo, dilute with methylene chloride (75 mL) and wash with saturated sodium hydrogen carbonate (35 mL). Extract the aqueous phase with methylene chloride (30 mL), wash combined organics with brine (30 mL) and dry (Na2SO4). Evaporate the solvent in vacuo and pass through a plug of silica gel to give 2-(carbomethoxy)indan as a yellow oil (3.98 g). Evaporate the solvent in vacuo dilute with methylene chloride (75 mL) wash with saturated sodium hydrogen carbonate (35 mL) Extract the aqueous phase with methylene chloride (30 mL) wash dry (Na2SO4) Evaporate the solvent in vacuo and pass through a plug of silica gel

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

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

Procedure: A solution of 20.4 g (164 mmoles) dimethyl methylphosphonate (Aldrich) in 200 ml dry tetrahydrofuran was cooled to -78° in a dry nitrogen atmosphere. To the stirred phosphonate solution was added 82.6 ml of 2.25M n-butyllithium in hexane solution (Alfa Inorganics, Inc.) dropwise over a period of 20 minutes at such a rate that the reaction temperature never rose above -65°. After an additional 5 minutes stirring at -78°, 14.0 g (73.5 mmole) methyl indane-2-carboxylate was added dropwise at a rate that kept the reaction temperature less than -70° (20 minutes). After 1.0 hour at -78° the reaction mixture was allowed to warm to ambient temperature, neutralized with 20 ml acetic acid and rotary evaporated to a white gel. The gelatinous material was taken up in 50 ml water, the aqueous phase extracted with 75 ml portions of methylene chloride (4x), the combined organic extracts were backwashed (75 ml H2O), dried (MgSO4), and concentrated (water aspirator) to a crude residue and distilled, b.p. 150°-160° (0.1 mm) to give 17.0 g (86.4%) dimethyl 2-oxo-2-(2-indany)ethylphsphonate (2i). the reaction temperature less than -70° (20 minutes) After 1.0 hour at -78° the reaction mixture was allowed rotary evaporated to a white gel the aqueous phase extracted with 75 ml portions of methylene chloride (4x) dried (MgSO4) concentrated (water aspirator) to a crude residue distilled

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

Procedure: A solution of 20.4 g (164 mmoles) dimethyl methylphosphonate (Aldrich) in 200 ml dry tetrahydrofuran was cooled to -78° in a dry nitrogen atmosphere. To the stirred phosphonate solution was added 82.6 ml of 2.25M n-butyllithium in hexane solution (Alfa Inorganics, Inc.) dropwise over a period of 20 minutes at such a rate that the reaction temperature never rose above -65°. After an additional 5 minutes stirring at -78°, 14.0 g (73.5 mmole) methyl indane-2-carboxylate was added dropwise at a rate that kept the reaction temperature less than -70° (20 minutes). After 1.0 hour at -78° the reaction mixture was allowed to warm to ambient temperature, neutralized with 20 ml acetic acid and rotary evaporated to a white gel. The gelatinous material was taken up in 50 ml water, the aqueous phase extracted with 75 ml portions of methylene chloride (4x), the combined organic extracts were backwashed (75 ml H2O), dried (MgSO4), and concentrated (water aspirator) to a crude residue and distilled, b.p. 150°-160° (0.1 mm) to give 17.0 g (86.4%) dimethyl 2-oxo-2-(2-indany)ethylphsphonate (2i). the reaction temperature less than -70° (20 minutes) After 1.0 hour at -78° the reaction mixture was allowed rotary evaporated to a white gel the aqueous phase extracted with 75 ml portions of methylene chloride (4x) dried (MgSO4) concentrated (water aspirator) to a crude residue distilled