2-(2-bromoethoxy)-2-methylpropane

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

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

Conditions: temp:20.01; pressure:0.00; stir:

Conditions: temp:20.01; pressure:0.00; stir:

Conditions: temp:20.01; pressure:0.00; stir:

Conditions: temp:20.01; pressure:0.00; stir:

Conditions: temp:20.01; pressure:0.00; stir:

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

Procedure: N′-(2-cyano-4-methoxy-5-[(2R)-pyrrolidin-2-ylmethoxy]phenyl)-N,N-dimethylimidoformamide (1.23 g, 4.06 mmol) in dimethylformamide (13 ml) was reacted with 2-(2-bromoethoxy)-2-methylpropane (809 mg, 4.47 mmol) in the presence of potassium carbonate (842 mg, 6.1 mmol) at 50° C. for 5 hours. The solvent was then evaporated, and the residue purified by chromatography on silica gel, eluting with dichloromethane:methanol (98:2) then (95:5), to yield N′-(5-{[(2R)-1-(2-tert-butoxyethyl)pyrrolidin-2-yl]methoxy}-2-cyano-4-methoxyphenyl)-N,N-dimethylimidoformamide (908 mg, 56% yield): The solvent was then evaporated the residue purified by chromatography on silica gel eluting with dichloromethane:methanol (98:2)

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

Procedure: 4-(2-hydroxyethyl)piperidine (1.94 g, 15 mmol) in dimethylformamide (20 ml) was reacted with 2-(2-bromoethoxy)-2-methylpropane (3.13 g, 17.3 mmol) at 50° C. for 15 hours. The mixture was cooled and the solid removed by filtration. The solid was washed with ethyl acetate and the organics were washed with water, dried (magnesium sulphate) and concentrated to give 2-(1-(2-tert-butoxy ethyl)piperidin-4-yl)ethanol as a yellow oil (2.35 g, 100% yield): The mixture was cooled the solid removed by filtration The solid was washed with ethyl acetate the organics were washed with water dried (magnesium sulphate) concentrated

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

Procedure: To a solution of hydrazine monohydrate (36.0 mL, 0.750 mol) in ethanol (70 mL) at 0° C. in an ice-water bath was added 2-(2-bromoethoxy)-2-methylpropane (12.1 mL, 0.075 mol) drop-wise over 20 minutes. The reaction was then allowed to warm to room temperature and stir for 5 minutes and then heated to 40° C. in a preheated oil bath for 4 hours. The reaction was then cooled to room temperature and concentrated to remove the ethanol. To the flask was added water (20 mL) and the aqueous layer was extracted with diethyl ether (2×100 mL). The organic layers were combined and dried over anhydrous Na2SO4, filtered and concentrated to provide (2-tert-butoxyethyl)-hydrazine as a colorless oil (6.05 g, 61%). heated to 40° C. in a preheated oil bath for 4 hours The reaction was then cooled to room temperature concentrated to remove the ethanol To the flask was added water (20 mL) the aqueous layer was extracted with diethyl ether (2×100 mL) dried over anhydrous Na2SO4 filtered concentrated

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

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