TERT-BUTYL-4-CHLORO-3-OXOBUTANOATE

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: treating t-butyl 4-chloro-3-oxobutanoate with sodium nitrite or nitrous acid to produce t-butyl 4-chloro-2-(Z)-hydroximino-3-oxobutanoate;

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

Procedure: A solution of 35.6 g of sodium nitrite in 100 ml of water was added to a cold solution of t-butyl 4-chloro-3-oxobutanoate (100.9 g, 0.439 moles of 84% material*) in 400 ml of acetic acid containing 50 ml of water over a 0.5 hour period with stirring. The mixture was stirred in the cold for an additional hour, then stored in the cold overnight. The mixture was diluted with 500 ml portions of water, 500 ml of saturated sodium bicarbonate, 500 ml of water and 500 ml of brine, then dried over magnesium sulfate and evaporated to give an amber oil; yield 88.6 g (91% yield). This material was used in the next step without further purification. *This compound was obtained from Lonza Chemical Co., Fair Lawn, N.J. The mixture was stirred in the cold for an additional hour stored in the cold overnight dried over magnesium sulfate evaporated to give an amber oil This material was used in the next step without further purification

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

Procedure: The procedure of example 369 was repeated using t-butyl-4-chloroacetoacetate as the substrate to give t-butyl-4-chloro-3(R)-hydroxybutyrate, [α]D23 +18.09° (c, 5.1 CHCl3).

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

Procedure: The procedure of example 369 was repeated using t-butyl-4-chloroacetoacetate as the substrate to give t-butyl-4-chloro-3(R)-hydroxybutyrate, [α]D23 +18.09° (c, 5.1 CHCl3).

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

Procedure: A solution of 35.6 g of sodium nitrite in 100 ml of water was added to a cold solution of t-butyl 4-chloro-3-oxobutanoate (100.9 g, 0.439 moles of 84% material*)inin 400 ml of acetic acid containing 50 ml of water over a 0.5 hour period with stirring. The mixture was stirred in the cold for an additional hour, then stored in the cold overnight. The mixture was diluted with 500 ml portions of water, 500 ml of saturated sodium bicarbonate, 500 ml of water and 500 ml of brine, then dried over magnesium sulfate and evaporated to give an amber oil; yield 88.6 g (91% yield). This material was used in the next step without further purification. The mixture was stirred in the cold for an additional hour stored in the cold overnight dried over magnesium sulfate evaporated to give an amber oil This material was used in the next step without further purification

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

Procedure: A solution of 35.6 g of sodium nitrite in 100 ml of water was added to a cold solution of t-butyl 4-chloro-3-oxobutanoate (100.9 g, 0.439 moles of 84% material*)inin 400 ml of acetic acid containing 50 ml of water over a 0.5 hour period with stirring. The mixture was stirred in the cold for an additional hour, then stored in the cold overnight. The mixture was diluted with 500 ml portions of water, 500 ml of saturated sodium bicarbonate, 500 ml of water and 500 ml of brine, then dried over magnesium sulfate and evaporated to give an amber oil; yield 88.6 g (91% yield). This material was used in the next step without further purification. The mixture was stirred in the cold for an additional hour stored in the cold overnight dried over magnesium sulfate evaporated to give an amber oil This material was used in the next step without further purification

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: 2.40 g (21.0 mmols) of dry potassium thioacetate were added to a solution, cooled to 0° C., of 3.85 g (20.0 mmols) of tert.-butyl 4-chloroacetoacetate in 40 ml of anhydrous acetonitrile and the mixture was stirred at this temperature for 30 minutes. Thereafter, the mixture was poured into a mixture of NaCl solution and ethyl acetate, the organic phase was separated off and extracted with 2×30 ml of ethyl acetate and the extracts were washed with water and dried over MgSO4. After the solvent had been evaporated off in vacuo and the residue had been chromatographed on 60 g of silica gel (toluene:ethyl acetate 95:5), 3.87 g (83%) of the title compound were obtained as a colorless oil, RF :0.2 (toluene:ethyl acetate 95:5). the organic phase was separated off extracted with 2×30 ml of ethyl acetate the extracts were washed with water dried over MgSO4 After the solvent had been evaporated off in vacuo the residue had been chromatographed on 60 g of silica gel (toluene:ethyl acetate 95:5)

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

Procedure: 2.40 g (21.0 mmols) of dry potassium thioacetate were added to a solution, cooled to 0° C., of 3.85 g (20.0 mmols) of tert.-butyl 4-chloroacetoacetate in 40 ml of anhydrous acetonitrile and the mixture was stirred at this temperature for 30 minutes. Thereafter, the mixture was poured into a mixture of NaCl solution and ethyl acetate, the organic phase was separated off and extracted with 2×30 ml of ethyl acetate and the extracts were washed with water and dried over MgSO4. After the solvent had been evaporated off in vacuo and the residue had been chromatographed on 60 g of silica gel (toluene:ethyl acetate 95:5), 3.87 g (83%) of the title compound were obtained as a colorless oil, RF :0.2 (toluene:ethyl acetate 95:5). the organic phase was separated off extracted with 2×30 ml of ethyl acetate the extracts were washed with water dried over MgSO4 After the solvent had been evaporated off in vacuo the residue had been chromatographed on 60 g of silica gel (toluene:ethyl acetate 95:5)