(4-aminophenyl) acetate

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

Procedure: 970 mg (6.4 mmol) of 4-acetoxyaniline, 50 ml of THF and 990 μl (7 mmol) of triethylamine were introduced into a round-bottomed flask. A solution of 3.2 g (6.4 mmol) of 4-[7-(1-adamantyl)-6-methoxyethoxy-methoxy-2-naphthyl]benzoic acid chloride in THF was added dropwise and the reaction mixture was stirred at room temperature for two hours. The reaction mixture was poured into water and extracted with ethyl acetate and the organic phase was separated by settling, dried over magnesium sulfate and evaporated. The residue obtained was triturated in heptane, filtered and dried. 3.15 g (81%) of the expected compound were collected, which compound had a melting point of 206°-7° C. extracted with ethyl acetate the organic phase was separated dried over magnesium sulfate evaporated The residue obtained was triturated in heptane filtered dried 3.15 g (81%) of the expected compound were collected

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

Procedure: 4-Hydroxydiphenylamine (m.p. 70° C., b.p. 330° C.) is formed by heating hydroquinone with aniline and zinc chloride at 180°-185° C. (G. Heller, Ann., 1919, 418, p. 265; A. Calm and M. Phillip, Chem. Ber., 1883, 16, p. 1799; 1884, 17, p. 2431), or by reaction of p-aminophenol with bromobenzene and cuprous iodide (German Pat. No. 187,870). 4-Amino-2-nitrophenol (dark red plates, m.p. 128° C.) can be prepared by the procedure described in A. Girard, Bull. Soc. Chim. Fr., 1924, 35, p. 773) and 4-Amino-3-nitrophenol (m.p. 154° C.), can be formed from the nitration of 4-aminophenyl acetate as described in (Girard, loc. cit.);

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

Procedure: 4-Hydroxydiphenylamine (m.p. 70° C., b.p. 330° C.) is formed by heating hydroquinone with aniline and zinc chloride at 180°-185° C. (G. Heller, Ann., 1919, 418, p. 265; A. Calm and M. Phillip, Chem. Ber., 1883, 16, p. 1799; 1884, 17, p. 2431), or by reaction of p-aminophenol with bromobenzene and cuprous iodide (German Pat. No. 187,870). 4-Amino-2-nitrophenol (dark red plates, m.p. 128° C.) can be prepared by the procedure described in A. Girard, Bull. Soc. Chim. Fr., 1924, 35, p. 773) and 4-Amino-3-nitrophenol (m.p. 154° C.), can be formed from the nitration of 4-aminophenyl acetate as described in (Girard, loc. cit.);

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

Procedure: Compound 55 was prepared in the manner of compound 12 substituting 4-nitrophenyl acetate for compound 11 in part C-1 of Example 1. Synthesis of 4-(2-chloroacetylamino)phenyl acetate (56):

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

Procedure: Compound 55 was prepared in the manner of compound 12 substituting 4-nitrophenyl acetate for compound 11 in part C-1 of Example 1. Synthesis of 4-(2-chloroacetylamino)phenyl acetate (56):

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

Procedure: [Step 1] 100 mg of 1-acetyl-4-oxo-2-methyl-1,2,3,4-tetrahydroquinoline and 227 mg of 4-acetoxyaniline were dissolved in 3 mL of toluene, and 250 μL of titanium tetrachloride (1.0 M dichloromethane solution) was added to the solution under ice cooling. The mixture was stirred for one hour under ice cooling, and then was stirred for another one hour at room temperature. After completion of the reaction, the reaction liquid was filtered through Celite and was concentrated under reduced pressure. The resulting residue was purified by using silica gel chromatography (chloroform), and thus 50 mg (30%) of 1-acetyl-2-methyl-4-[(4-acetoxyphenyl)imino]-1,2,3,4-tetrahydroquinoline was obtained as a yellow soup-like substance. was stirred for another one hour at room temperature After completion of the reaction the reaction liquid was filtered through Celite was concentrated under reduced pressure The resulting residue was purified

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

Procedure: Using general procedure A, 1-Boc-4-piperidone (2.52 g, 12.66 mmol) and acetic acid 4-amino-phenyl ester (Bargota, Rakesh S.; et al., Bioorg. Med. Chem. Lett., 13, 10, 2003, 1623-1626) (2.95 g, 19.52 mmol) afforded 4-(4-acetoxy-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester as a white solid (3.41 g, 76%).

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

Procedure: [Step 1] 100 mg of 1-acetyl-4-oxo-2-methyl-1,2,3,4-tetrahydroquinoline and 227 mg of 4-acetoxyaniline were dissolved in 3 mL of toluene, and 250 μL of titanium tetrachloride (1.0 M dichloromethane solution) was added to the solution under ice cooling. The mixture was stirred for one hour under ice cooling, and then was stirred for another one hour at room temperature. After completion of the reaction, the reaction liquid was filtered through Celite and was concentrated under reduced pressure. The resulting residue was purified by using silica gel chromatography (chloroform), and thus 50 mg (30%) of 1-acetyl-2-methyl-4-[(4-acetoxyphenyl)imino]-1,2,3,4-tetrahydroquinoline was obtained as a yellow soup-like substance. was stirred for another one hour at room temperature After completion of the reaction the reaction liquid was filtered through Celite was concentrated under reduced pressure The resulting residue was purified

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

Procedure: Compound 56 was prepared in the manner of compound 3 substituting compound 55 for compound 1 in part A of Example 1.

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

Procedure: Compound 55 was prepared in the manner of compound 12 substituting 4-nitrophenyl acetate for compound 11 in part C-1 of Example 1.

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

Procedure: 970 mg (6.4 mmol) of 4-acetoxyaniline, 50 ml of THF and 990 μl (7 mmol) of triethylamine were introduced into a round-bottomed flask. A solution of 3.2 g (6.4 mmol) of 4-[7-(1-adamantyl)-6-methoxyethoxy-methoxy-2-naphthyl]benzoic acid chloride in THF was added dropwise and the reaction mixture was stirred at room temperature for two hours. The reaction mixture was poured into water and extracted with ethyl acetate and the organic phase was separated by settling, dried over magnesium sulfate and evaporated. The residue obtained was triturated in heptane, filtered and dried. 3.15 g (81%) of the expected compound were collected, which compound had a melting point of 206°-7° C. extracted with ethyl acetate the organic phase was separated dried over magnesium sulfate evaporated The residue obtained was triturated in heptane filtered dried 3.15 g (81%) of the expected compound were collected

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

Procedure: 4-Hydroxydiphenylamine (m.p. 70° C., b.p. 330° C.) is formed by heating hydroquinone with aniline and zinc chloride at 180°-185° C. (G. Heller, Ann., 1919, 418, p. 265; A. Calm and M. Phillip, Chem. Ber., 1883, 16, p. 1799; 1884, 17, p. 2431), or by reaction of p-aminophenol with bromobenzene and cuprous iodide (German Pat. No. 187,870). 4-Amino-2-nitrophenol (dark red plates, m.p. 128° C.) can be prepared by the procedure described in A. Girard, Bull. Soc. Chim. Fr., 1924, 35, p. 773) and 4-Amino-3-nitrophenol (m.p. 154° C.), can be formed from the nitration of 4-aminophenyl acetate as described in (Girard, loc. cit.);