2-[(2-methylpropan-2-yl)oxy]acetic acid

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 3-neck 500 ml round-bottom flask equipped with a magnetic stirrer, reflux condenser and addition funnel was added (1,1-dimethylethoxy)acetic acid (24.00 g, 0.182 moles) and 300 ml of toluene under nitrogen. Oxalyl chloride (46.10 g, 0.363 moles) was then added dropwise and to this mixture was added N,N-dimethylformamide (0.25 g, 0.003 moles). This solution was heated at 30°-40° C. for 5 hours and then concentrated in vacuo to give 14.5 g of the product as a brown oil. To a 3-neck 500 ml round-bottom flask equipped with a magnetic stirrer reflux condenser and addition funnel This solution was heated at 30°-40° C. for 5 hours concentrated in vacuo

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

Procedure: To a 3-neck 2-liter round-bottom flask equipped with a mechanical stirrer, reflux condenser and addition funnel was added potassium tert-butoxide (100.00 g, 0.891 moles) and 1500 ml of toluene under nitrogen. A solution of bromoacetic acid (61.90 g, 0.446 moles) in 100 ml of toluene was then added dropwise and the mixture then heated at reflux for 24 hours. After cooling the mixture to room temperature, water (100 ml) was added and the layers separated. The aqueous layer was washed with ether (2×50 ml) and then acidified to pH 1 with concentrated hydrochloric acid. The resulting mixture was extracted with ether (3×100 ml) and the combined extracts washed with saturated sodium chloride solution (1×75 ml), dried over magnesium sulfate and concentrated in vacuo to give 27.3 g of the product as a yellow oil. To a 3-neck 2-liter round-bottom flask equipped with a mechanical stirrer reflux condenser and addition funnel the mixture then heated at reflux for 24 hours the layers separated The aqueous layer was washed with ether (2×50 ml) The resulting mixture was extracted with ether (3×100 ml) the combined extracts washed with saturated sodium chloride solution (1×75 ml) dried over magnesium sulfate concentrated in vacuo

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

Procedure: Oxazoles and Oxazolines Yokokawa (Synthetic Lett., 1992, 2, 153) has recently described the preparation and cyclization of N-acylserine ester derivatives to give 2-substituted-4,5-dihydrooxazole-4-carboxylate esters which, after oxidation, give the corresponding 2-substituted-oxazole-4-carboxylate esters. By inference, N-acylation of serine methyl ester with t-butoxyacetic acid, followed by cyclization, oxidation, deprotection and conversion to the chloride by standard methods should give methyl 2-(chloromethyl)oxazole-4-carboxylate, as outlined in Scheme XX below. Eliminiation of the oxidation step will give the corresponding oxazoline. ##STR52##

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

Procedure: A suspension of sodium t-butoxide (24.1 g) in t-butanol (150 ml) was cooled in a water bath and treated drop-wise with a solution of chloroacetic acid (11.4 g) in t-butanol (30 ml). The mixture was heated under reflux for 5 h then concentrated in vacuo. The resultant white solid was dried in vacuo for 16 h then water (10 ml) was added and the mixture was filtered. The filtrate was treated with diethyl ether (150 ml), then cooled in an ice bath, stirred and acidified to pH1 with 2N sulphuric acid. The layers were separated and the aqueous layer was further extracted with diethyl ether. The combined organic extracts were dried MgSO4) and concentrated in vacuo to afford Intermediate 32 (11.1 g). 1H NMR (400 MHz, CDCl3, δ ppm) 1.27 (9H, s), 4.04 (2H, s). was cooled in a water bath The mixture was heated under reflux for 5 h then concentrated in vacuo The resultant white solid was dried in vacuo for 16 h water (10 ml) was added the mixture was filtered The filtrate was treated with diethyl ether (150 ml) cooled in an ice bath The layers were separated the aqueous layer was further extracted with diethyl ether concentrated in vacuo

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

Procedure: A suspension of sodium t-butoxide (24.1 g) in t-butanol (150 ml) was cooled in a water bath and treated drop-wise with a solution of chloroacetic acid (11.4 g) in t-butanol (30 ml). The mixture was heated under reflux for 5 h then concentrated in vacuo. The resultant white solid was dried in vacuo for 16 h then water (10 ml) was added and the mixture was filtered. The filtrate was treated with diethyl ether (150 ml), then cooled in an ice bath, stirred and acidified to pH1 with 2N sulphuric acid. The layers were separated and the aqueous layer was further extracted with diethyl ether. The combined organic extracts were dried MgSO4) and concentrated in vacuo to afford Intermediate 32 (11.1 g). 1H NMR (400 MHz, CDCl3, δ ppm) 1.27 (9H, s), 4.04 (2H, s). was cooled in a water bath The mixture was heated under reflux for 5 h then concentrated in vacuo The resultant white solid was dried in vacuo for 16 h water (10 ml) was added the mixture was filtered The filtrate was treated with diethyl ether (150 ml) cooled in an ice bath The layers were separated the aqueous layer was further extracted with diethyl ether concentrated in vacuo

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

Procedure: To a 3-neck 500 ml round-bottom flask equipped with a magnetic stirrer, reflux condenser and addition funnel was added (1,1-dimethylethoxy)acetic acid (24.00 g, 0.182 moles) and 300 ml of toluene under nitrogen. Oxalyl chloride (46.10 g, 0.363 moles) was then added dropwise and to this mixture was added N,N-dimethylformamide (0.25 g, 0.003 moles). This solution was heated at 30°-40° C. for 5 hours and then concentrated in vacuo to give 14.5 g of the product as a brown oil. To a 3-neck 500 ml round-bottom flask equipped with a magnetic stirrer reflux condenser and addition funnel This solution was heated at 30°-40° C. for 5 hours concentrated in vacuo

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

Procedure: To a 3-neck 2-liter round-bottom flask equipped with a mechanical stirrer, reflux condenser and addition funnel was added potassium tert-butoxide (100.00 g, 0.891 moles) and 1500 ml of toluene under nitrogen. A solution of bromoacetic acid (61.90 g, 0.446 moles) in 100 ml of toluene was then added dropwise and the mixture then heated at reflux for 24 hours. After cooling the mixture to room temperature, water (100 ml) was added and the layers separated. The aqueous layer was washed with ether (2×50 ml) and then acidified to pH 1 with concentrated hydrochloric acid. The resulting mixture was extracted with ether (3×100 ml) and the combined extracts washed with saturated sodium chloride solution (1×75 ml), dried over magnesium sulfate and concentrated in vacuo to give 27.3 g of the product as a yellow oil. To a 3-neck 2-liter round-bottom flask equipped with a mechanical stirrer reflux condenser and addition funnel the mixture then heated at reflux for 24 hours the layers separated The aqueous layer was washed with ether (2×50 ml) The resulting mixture was extracted with ether (3×100 ml) the combined extracts washed with saturated sodium chloride solution (1×75 ml) dried over magnesium sulfate concentrated in vacuo

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

Procedure: To 100 ml of a 50:50 (v/v) methanol/water solution containing 14.35 g of potassium carbonate, was added n-butyl 2-tert-butoxyacetate (6.50 g, 0.0346 mol). The mixture was heated at reflux for 17 hours and the volatiles removed on a flash evaporator. The remaining solution was cooled to approximately 0° C. and acidified to pH 3-4 with cold 50% aqueous hydrogen chloride. The product was extracted with ether, the ether extract washed with brine and dried over magnesium sulfate, then concentrated in vacuo to give the title compound as a yellow liquid. The mixture was heated at reflux for 17 hours the volatiles removed on a flash evaporator The product was extracted with ether the ether extract washed with brine dried over magnesium sulfate concentrated in vacuo

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

Procedure: To 100 ml of a 50:50 (v/v) methanol/water solution containing 14.35 g of potassium carbonate, was added n-butyl 2-tert-butoxyacetate (6.50 g, 0.0346 mol). The mixture was heated at reflux for 17 hours and the volatiles removed on a flash evaporator. The remaining solution was cooled to approximately 0° C. and acidified to pH 3-4 with cold 50% aqueous hydrogen chloride. The product was extracted with ether, the ether extract washed with brine and dried over magnesium sulfate, then concentrated in vacuo to give the title compound as a yellow liquid. The mixture was heated at reflux for 17 hours the volatiles removed on a flash evaporator The product was extracted with ether the ether extract washed with brine dried over magnesium sulfate concentrated in vacuo