(1-chloro-2-methylpropyl) 2,2-dimethylpropanoate

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

Procedure: A mixture of the title A compound of Example 28, 2-cyclopropyl-3-[[2'-[2-(triphenylmethyl)-2H-tetrazol-5-yl][1,1'-biphenyl]-4-yl]oxy]-4-quinolinecarboxylic acid (1.55 mmol), the title B compound of Example 16, 2,2-dimethylpropanoic acid, 1-chloro-2-methylpropyl ester (1.09 g, 6.65 mmol), potassium carbonate (521 mg, 3.77 mmol), potassium iodide (375 mg, 2.26 mmol), and 18-crown-6 (100 mg, 0.378 mmol) in dimethylformamide (3.7 mL) was heated at 90° C. for 2.5 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (75 mL) and filtered. The organic filtrate was rinsed with aq. 5% sodium bisulfite and brine, dried (magnesium sulfate), and concentrated in vacuo to give a crude product (2 g). Flash chromatography on silica gel (60 g) eluted with 1 column volume of hexanes followed by 1.8 L of 12:1, then 900 mL of 8:1, hexanes:ethyl acetate yielded the title compound (950 mg, 72%). filtered The organic filtrate was rinsed with aq. 5% sodium bisulfite and brine dried (magnesium sulfate) concentrated in vacuo to give a crude product (2 g) Flash chromatography on silica gel (60 g) eluted with 1 column volume of hexanes

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

Procedure: To freshly fused zinc chloride (70 mg) and trimethylacetylchloride (12.3 mL, 100 mmol) cooled in an ice bath in dichloromethane (25 mL) was added isobutyraldehyde (9.08 mL, 100 mmol), keeping the reaction temperature <25° C. The solution was allowed to warm to room temperature and stirred one hour, washed with a solution of sodium acetate (50 mL, 20%), dried (magnesium sulfate), and concentrated under low vacuum to remove dichloromethane (yield 16.18 g, 84 mmol, 84%). the reaction temperature <25° C washed with a solution of sodium acetate (50 mL, 20%) dried (magnesium sulfate) concentrated under low vacuum

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

Procedure: To freshly fused zinc chloride (27.3 mg) and trimethylacetylchloride (5.11 ml, 41.5 mmol) in methylene chloride(10 ml) at 10° C. was added isobutyraldehyde (freshly distilled) (3.77 ml, 41.5 mmol) dropwise, maintaining the temperature at <25° C. Once the addition was complete, the reaction was stirred for one hour at room temperature. The reaction mixture was then washed with 20% NaOAc, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give the title A compound (3.25 g) as a clear liquid. freshly distilled) (3.77 ml, 41.5 mmol) dropwise maintaining the temperature at <25° C Once the addition The reaction mixture was then washed with 20% NaOAc dried over anhydrous magnesium sulfate filtered concentrated in vacuo