3-chloro-4-methylaniline

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:

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:

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

Procedure: A mixture of 3-chloro-4-methylaniline (7.79 g, 55 mmol), 1-chloro-3-iodopropane (5.91 ml, 55 mmol), cesium carbonate (35.84 g, 110 mmol) and DMF (15 ml) was stirred at room temperature for 19 hours. To the mixture was added water (75 ml), and the mixture was extracted with hexane (60 ml, 30 ml×2). The organic layer was washed with water (10 ml), dried over magnesium sulfate and concentrated under reduced pressure. The concentrate was subjected to column chromatography (silica gel 200 g, hexane/ethyl acetate=1/0 to 19/1), and the desired fraction was concentrated under reduced pressure to give the titled compound (7.30 g, 33 mmol, Yield 61%) as a pale brown oily substance. the mixture was extracted with hexane (60 ml, 30 ml×2) The organic layer was washed with water (10 ml) dried over magnesium sulfate concentrated under reduced pressure the desired fraction was concentrated under reduced pressure

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

Procedure: According to example 234, 3-chloro-4-methylaniline (21.5 g, 150 mmol) was reacted with triethyl orthoformate, ethyl nitroacetate and acetic acid followed by treatment with triethyl orthoformate, iron and acetic acid and subsequent alkaline hydrolysis. The isolated acid (10.0 g) was directly reduced according to example 264, by reaction with BH3 THF complex followed by hydrolytic workup and the title compound was obtained as a white crystalline solid (5.2 g, 16%). Mp. 126-133° C. (AcOEt/hexane), MS: m/e=222 (M+)

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

Procedure: 3-Chloro-4-methylaniline (10.26 g, 72.5 mmol), sodium hydrogen carbonate (9.1 g, 108 mmol) and bromoacetaldehyde diethyl acetal (13.1 ml, 87.1 mmol) were stirred at reflux under Ar in ethanol (150 ml) for 6 days. The mixture was then evaporated to dryness, partitioned between ether and water, and separated. The organic portion was washed with brine, dried (Na2SO4) and evaporated to a black oil. Bulb to bulb distillation of this crude material (oven temperature 175° C., ca 0.1 mmHg) then gave the title compound (4.90 g, 26%) as a colourless oil. The mixture was then evaporated to dryness partitioned between ether and water separated The organic portion was washed with brine dried (Na2SO4) evaporated to a black oil Bulb to bulb distillation of this crude material (oven temperature 175° C., ca 0.1 mmHg)

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