methylidenecyclobutane

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: To a solution of methylenecyclobutane (2 mL, 21.6 mmol) in ethyl acetate (125 mL) was added (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (6.55 g, 43.2 mmol) and solid sodium bicarbonate (16.3 g, 194 mmol). The reaction mixture was sealed and stirred at room temperature for 6 hours. More (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (4 g, 26.4 mmol) and sodium bicarbonate (8 g, 95.2 mmol) were added and the reaction was stirred at room temperature for an additional 12 hours. The reaction was diluted with ethyl acetate and washed successively with water and brine, dried (MgSO4) and concentrated to yield crude 5-oxa-6-aza-spiro[3.4]oct-6-ene-7-carboxylic acid ethyl ester, contaminated with (Z)-Ethyl 2-chloro-2-(hydroxyimino)acetate and related compounds. The reaction mixture was sealed the reaction was stirred at room temperature for an additional 12 hours washed successively with water and brine dried (MgSO4) concentrated

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

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

Procedure: A stirred mixture of benzene (5.0 ml, 56 mmol) and Sulfuric acid (1.17 ml, 21.9 mmol) was cooled to 0° C. and treated dropwise with a solution of Methylenecyclobutane (1.00 ml, 10.8 mmol) in Benzene (3.0 ml, 34 mmol) over-1 h. Upon completion of the addition, the reaction mixture was stirred an additional 1 h while being warmed to RT. The mixture extracted with 15 ml of hexane. The organic phase was washed with 10 ml H2O and 10 ml sat NaHCO3, dried over Na2SO4, filtered and concentrated to yield a colorless liquid. The liquid was purified by kugelrohr distillation (5-10 torr) to yield the desired compound as a colourless liquid. First fraction was collected at 75-85° C. as a colorless liquid (330 mg) of product as a colorless liquid. Upon completion of the addition while being warmed to RT The mixture extracted with 15 ml of hexane The organic phase was washed with 10 ml H2O and 10 ml dried over Na2SO4 filtered concentrated to yield a colorless liquid The liquid was purified by kugelrohr distillation (5-10 torr)

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

Procedure: A stirred mixture of benzene (5.0 ml, 56 mmol) and Sulfuric acid (1.17 ml, 21.9 mmol) was cooled to 0° C. and treated dropwise with a solution of Methylenecyclobutane (1.00 ml, 10.8 mmol) in Benzene (3.0 ml, 34 mmol) over-1 h. Upon completion of the addition, the reaction mixture was stirred an additional 1 h while being warmed to RT. The mixture extracted with 15 ml of hexane. The organic phase was washed with 10 ml H2O and 10 ml sat NaHCO3, dried over Na2SO4, filtered and concentrated to yield a colorless liquid. The liquid was purified by kugelrohr distillation (5-10 torr) to yield the desired compound as a colourless liquid. First fraction was collected at 75-85° C. as a colorless liquid (330 mg) of product as a colorless liquid. Upon completion of the addition while being warmed to RT The mixture extracted with 15 ml of hexane The organic phase was washed with 10 ml H2O and 10 ml dried over Na2SO4 filtered concentrated to yield a colorless liquid The liquid was purified by kugelrohr distillation (5-10 torr)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of tert-butyl (2S,3S)-2-(tert-butyldimethylsilyloxy)-1-hydroxyhex-5-en-3-ylcarbamate (1.0 g, 2.9 mmol) and Grubbs Catalyst 2nd generation (0.12 g, 0.14 mmol) in DCE (6 mL) was treated with methylenecyclobutane (0.79 g, 12 mmol) and heated to 80° C. in a sealed vial overnight. The reaction mixture was diluted with EtOAc, washed with saturated NaHCO3 solution, and brine. The organics were dried over MgSO4 and concentrated under reduced pressure. Purification of the crude residue by column chromatography gave tert-butyl (2S,3S)-2-(tert-butyldimethylsilyloxy)-5-cyclobutylidene-1-hydroxypentan-3-ylcarbamate (0.900 g, 81% yield) as a 2:1 mixture with starting alkene. washed with saturated NaHCO3 solution, and brine The organics were dried over MgSO4 concentrated under reduced pressure Purification of the crude residue by column chromatography

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

Procedure: To a solution of methylenecyclobutane (2 mL, 21.6 mmol) in ethyl acetate (125 mL) was added (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (6.55 g, 43.2 mmol) and solid sodium bicarbonate (16.3 g, 194 mmol). The reaction mixture was sealed and stirred at room temperature for 6 hours. More (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (4 g, 26.4 mmol) and sodium bicarbonate (8 g, 95.2 mmol) were added and the reaction was stirred at room temperature for an additional 12 hours. The reaction was diluted with ethyl acetate and washed successively with water and brine, dried (MgSO4) and concentrated to yield crude 5-oxa-6-aza-spiro[3.4]oct-6-ene-7-carboxylic acid ethyl ester, contaminated with (Z)-Ethyl 2-chloro-2-(hydroxyimino)acetate and related compounds. The reaction mixture was sealed the reaction was stirred at room temperature for an additional 12 hours washed successively with water and brine dried (MgSO4) concentrated

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

Procedure: To a solution of methylenecyclobutane (2 mL, 21.6 mmol) in ethyl acetate (125 mL) was added (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (6.55 g, 43.2 mmol) and solid sodium bicarbonate (16.3 g, 194 mmol). The reaction mixture was sealed and stirred at room temperature for 6 hours. More (Z)-ethyl 2-chloro-2-(hydroxyimino)acetate (4 g, 26.4 mmol) and sodium bicarbonate (8 g, 95.2 mmol) were added and the reaction was stirred at room temperature for an additional 12 hours. The reaction was diluted with ethyl acetate and washed successively with water and brine, dried (MgSO4) and concentrated to yield crude 5-oxa-6-aza-spiro[3.4]oct-6-ene-7-carboxylic acid ethyl ester, contaminated with (Z)-Ethyl 2-chloro-2-(hydroxyimino)acetate and related compounds. The reaction mixture was sealed the reaction was stirred at room temperature for an additional 12 hours washed successively with water and brine dried (MgSO4) concentrated

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

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