3-methylbutyl nitrate

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 solution of ethyl 2-amino-5-phenylthiazole-4-carboxylate in MeCN was added CuCl2 at 0° C., and the isoamyl nitrate was slowly added dropwise thereto, followed by stirring for 1 hour. To the reaction mixture was added CHCl3, followed by stirring at 0° C. for 2 hours and then at room temperature for 2 hours. The reaction mixture was neutralized by addition of a 1 M aqueous NaOH solution, and filtered through Celite. The filtrate was extracted with EtOAc, and the organic layer was washed with water and brine in this order and then dried over MgSO4. After concentration under reduced pressure, the residue obtained was purified by medium-pressure preparative liquid chromatography (silica gel YAMAZEN YFLC WPrep2XY, hexane:EtOAc) to obtain ethyl 2-chloro-5-phenylthiazole-4-carboxylate as a yellow oil. by stirring at 0° C. for 2 hours at room temperature for 2 hours filtered through Celite The filtrate was extracted with EtOAc the organic layer was washed with water and brine in this order dried over MgSO4 After concentration under reduced pressure the residue obtained was purified by medium-pressure preparative liquid chromatography (silica gel YAMAZEN YFLC WPrep2XY, hexane:EtOAc)

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

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

Procedure: 3-Chloro-3-methyl-2-nitroso-1-(5-methyl-2-nitro-1H-imidazol-1-yl) butane was prepared in 60% yield from 1-(5-methyl-2-nitro-1H-imidazol-1-yl)-3-methyl-2-butene (1.0 g, 5.12 mmol, Example 27), isoamyl nitrate (5.0 mL) and concentrated HCl (5.0 mL) following the procedure described for the preparation of its positional isomer (Example 27B) as a light blue solid; mp. 102-105° C. (decomp); 1H NMR (DMSO-d6) δ 1.73 [s, 6H, C(CH3)2], 2.32(s, 3H, imi-CH3), 5.53(s, 2H, NCH2), 6.97 ( s. 1H, imi-CH) and 11.58 (s, 1H, NOH). MS m/e 261 (M+H)+. described for the preparation of its positional isomer (Example 27B) as a light blue solid

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

Procedure: 3-Chloro-3-methyl-2-nitroso-1-(5-methyl-2-nitro-1H-imidazol-1-yl) butane was prepared in 60% yield from 1-(5-methyl-2-nitro-1H-imidazol-1-yl)-3-methyl-2-butene (1.0 g, 5.12 mmol, Example 27), isoamyl nitrate (5.0 mL) and concentrated HCl (5.0 mL) following the procedure described for the preparation of its positional isomer (Example 27B) as a light blue solid; mp. 102-105° C. (decomp); 1H NMR (DMSO-d6) δ 1.73 [s, 6H, C(CH3)2], 2.32(s, 3H, imi-CH3), 5.53(s, 2H, NCH2), 6.97 ( s. 1H, imi-CH) and 11.58 (s, 1H, NOH). MS m/e 261 (M+H)+. described for the preparation of its positional isomer (Example 27B) as a light blue solid

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

Procedure: A mixture of 180 mg. of 5-amino-2-phenyloxazolo[ 5,4-b]pyridine, 10 ml. of benzene and 0.2 ml. of isoamyl nitrate was refluxed for 11/2 hours. The hot solution was filtered and concentrated to dryness. The residue was extracted with ether and the extract was filtered through aluminum oxide and concentrated to dryness. The crystalline residue was recrystallized from ethyl acetate to give 2,5-diphenyloxazolo[ 5,4-b]pyridine, m.p. 151°-152° C. A mixture of 180 mg The hot solution was filtered concentrated to dryness The residue was extracted with ether the extract was filtered through aluminum oxide concentrated to dryness The crystalline residue was recrystallized from ethyl acetate

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

Procedure: A mixture of 180 mg. of 5-amino-2-phenyloxazolo[ 5,4-b]pyridine, 10 ml. of benzene and 0.2 ml. of isoamyl nitrate was refluxed for 11/2 hours. The hot solution was filtered and concentrated to dryness. The residue was extracted with ether and the extract was filtered through aluminum oxide and concentrated to dryness. The crystalline residue was recrystallized from ethyl acetate to give 2,5-diphenyloxazolo[ 5,4-b]pyridine, m.p. 151°-152° C. A mixture of 180 mg The hot solution was filtered concentrated to dryness The residue was extracted with ether the extract was filtered through aluminum oxide concentrated to dryness The crystalline residue was recrystallized from ethyl acetate

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

Procedure: The starting material was obtained using a similar procedure to that described for that in Example 9, but starting with 2-(2-methylthien-5-ylthio)acetic acid (described in Zh. Obsch. Khim. 1959, 29, 3631; 8.87 g), adding the butyllithium in hexane at -30° C. and the isoamyl nitrate at 0° C. The product 2-methyl-5-(nitromethylthio)thiophene, was obtained as an oil in 9% yield after column chromatography eluting with 10% ethyl acetate/hexane; NMR: 2.48 (s,3H), 5.38 (s,2H), 6.7 (m,1H), 7.1 (d,1H). The starting material was obtained at 0° C

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

Procedure: The starting material was obtained using a similar procedure to that described for that in Example 9, but starting with 2-(2-methylthien-5-ylthio)acetic acid (described in Zh. Obsch. Khim. 1959, 29, 3631; 8.87 g), adding the butyllithium in hexane at -30° C. and the isoamyl nitrate at 0° C. The product 2-methyl-5-(nitromethylthio)thiophene, was obtained as an oil in 9% yield after column chromatography eluting with 10% ethyl acetate/hexane; NMR: 2.48 (s,3H), 5.38 (s,2H), 6.7 (m,1H), 7.1 (d,1H). The starting material was obtained at 0° C

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A hexane/THF solution of lithium diisopropylamide was obtained by adding butyllithium (1.55 M hexane solution, 86.45 ml) to a stirred solution of diisopropylamine (101 g) in THF (100 ml) at -70° C. under an argon atmosphere. After 1 hour at -70° C., a solution of 2-(2-methoxythien-5-ylthio)acetic acid (obtained as described in West German OLS no. 1512272; 10.91 g) was added to the diisopropylamide solution during 20 minutes at -70° C. After 2 hours at this temperature, it was allowed to warm up to -40° C. Isoamyl nitrate (21.2 ml) was then added. The mixture was stirred at -40° C. for 2 hours and then at ambient temperature for 16 hours. The mixture was acidified to pH 2 with 2 M hydrochloric acid and stirred for 1 hour, during which time the intermediate 2-nitro-2-(2-methoxythien-5-ylthio)acetic acid underwent decarboxylation. The mixture was added to water (100 ml) and extracted with ethyl acetate. The combined organic layers were washed first with saturated sodium bicarbonate solution (200 ml) (to remove unreacted acidic starting material) and then with 2 M sodium hydroxide (2×200 ml). The latter washings were acidified to pH 2 with 2 M hydrochloric acid and extracted with ether (2×300 ml). The combined extracts were dried (MgSO4) in the presence of activated charcoal and evaporated. The residual oil was purified by column chromatography on silica (300 g) using 15% v/v ethyl acetate/hexane as eluant to give 2-methoxy-5-(nitromethylthio)thiophene (2.9 g) as an oil; NMR (90 MHz): 3.9 (s,3H), 5.25 (s,2H), 6.1 (d,1H), 7.0 (d,1H). at ambient temperature for 16 hours extracted with ethyl acetate The combined organic layers were washed first with saturated sodium bicarbonate solution (200 ml) (to remove unreacted acidic starting material) extracted with ether (2×300 ml) The combined extracts were dried (MgSO4) in the presence of activated charcoal evaporated The residual oil was purified by column chromatography on silica (300 g)