4-hydroxybutan-2-one

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: The title compound was prepared according to the method of Example 460 starting with 2-(4-fluorophenyl)-4-hydroxy-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 2-(3,4-difluorophenyl)-4-hydroxy-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone and substituting 4-hydroxy-2-butanone in place of acetol. (yield: 85.0 mg, 20%). mp 133-136° C.; 1H NMR (300 MHz, CDCl3) δ 2.04 (s, 3H), 2.80 (t, J=9 Hz, 2H), 3.13 (s, 3H), 4.76 (t, J=9 Hz, 2H), 7.20 (t, J=9 Hz, 2H), 7.55 (m, 2H), 7.55 (d, J=9 Hz, 2H), 7.91 (s, 1H), 8.05 (d, J=9 Hz, 2H). MS (DCI/NH3) m/z 431 (M+H)+, 448 (M+NH4)+. Anal. calc. for C21H19FN2O5S: C, 58.60; H, 4.42; N, 6.52. Found: C, 58.87; H, 4.55; N, 6.51.

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

Procedure: In the manner described in Example 1, 3.80 g (25 mmol) samples of trimethylhydroquinone were treated in 25 ml of methanol, 5.0 ml of trimethyl orthoformate, and 0.10 ml of 36 N aqueous H 2 SO 4 with 50 mmole portions of the following methyl vinyl ketone substitutes: (a), 2-methoxybutadiene; (b), 3-ketobutanol, (c), 3,3-dimethoxybutene (contaminated with about 20 percent 2-methoxybutadiene); and (d), 4-methoxy-2 -butanone. The reactions were monitored by tlc. Reactions (a),(c) and (d) were complete after 24 hr and were worked up and dried in the manner of Example 1 to give (±)-6-hydroxy-2-methoxy-2,5,7,8 -tetramethylchroman. In reaction (b), a>50 percent conversion to (±)-6-hydroxy-2-methoxy-2,5,7,8-tetramethylchroman was indicated by tlc. dried in the manner of Example 1

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

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

Procedure: In the manner described in Example 1, 3.80 g (25 mmol) samples of trimethylhydroquinone were treated in 25 ml of methanol, 5.0 ml of trimethyl orthoformate, and 0.10 ml of 36 N aqueous H2SO4 with 50 mmole portions of the following methyl vinyl ketone substitutes: a, 2-methoxybutadiene; b, 3-ketobutanol; c, 3,3-dimethoxybutene (contaminated with about 20 percent 2-methoxybutadiene); and d, 4-methoxy-2-butanone. The reactions were monitored by tlc. Reactions a,c and d were complete after 24 hr and were worked up and dried in the manner of Example 1 to give (±)-6-hydroxy-2-methoxy-2,5,7,8-tetramethylchroman. In reaction b, a>50 percent conversion to (±)-6-hydroxy-2-methoxy-2,5,7,8-tetramethylchroman was indicated by tlc. dried in the manner of Example 1

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

Procedure: In the manner described in Example 1, 3.80 g (25 mmol) samples of trimethylhydroquinone were treated in 25 ml of methanol, 5.0 ml of trimethyl orthoformate, and 0.10 ml of 36 N aqueous H2SO4 with 50 mmole portions of the following methyl vinyl ketone substitutes: a, 2-methoxybutadiene; b, 3-ketobutanol; c, 3,3-dimethoxybutene (contaminated with about 20 percent 2-methoxybutadiene); and d, 4-methoxy-2-butanone. The reactions were monitored by tlc. Reactions a,c and d were complete after 24 hr and were worked up and dried in the manner of Example 1 to give (±)-6-hydroxy-2-methoxy-2,5,7,8-tetramethylchroman. In reaction b, a>50 percent conversion to (±)-6-hydroxy-2-methoxy-2,5,7,8-tetramethylchroman was indicated by tlc. dried in the manner of Example 1

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

Procedure: To a mixture of 3-(1-methylindol-3-yl)-4-(3-aminophenyl)-1H-pyrrole-2,5-dione (0.2 g, 0.6 mmol) and 4-hydroxy-2-butanone (80 mg, 1.5 eq) in dichloromethane (15 mL) was added NaCNBH3 (56 mg, 1.5 eq) and the reaction mixture was stirred at RT for three days. The product 3-(1-methylindol-3-yl)-4-[3-(3-hydroxy-1-methylpropylamino)phenyl]-1H-pyrrole-2,5-dione separated by preparatory TLC (8.9 mg, 3.6%). LC/mS: M+ 389. The product 3-(1-methylindol-3-yl)-4-[3-(3-hydroxy-1-methylpropylamino)phenyl]-1H-pyrrole-2,5-dione separated by preparatory TLC (8.9 mg, 3.6%)

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

Procedure: To 400 ml of tetrahydrofuran in a reactor, 15.0 g (0.17 mol) of 3-oxo-1-butanol and 26.3 g (0.19 mol) of benzoyl chloride were dissolved, followed by drop-wise adding 20.6 g (0.20 mol) of triethylamine under ice-cooling. After the end of drop-wise addition, the reaction liquid was stirred at room temperature for 3 hours. Hydrochloric acid salt of triethylamine was filtered, followed by adding water to the filtrate and extracting with ethyl acetate. The organic layer was washed with water, a saturated aqueous solution of sodium carbonate, water and a saturated saline solution in this order, followed by drying over anhydrous magnesium sulfate and concentrating under reduced pressure. The residue was purified with silica gel column chromatography (ethyl acetate:hexane=1:5 to 1:3) to obtain 31.5 g (yield: 96%) of 3-oxobutylbenzoate. cooling After the end of drop-wise addition the reaction liquid Hydrochloric acid salt of triethylamine was filtered by adding water to the filtrate extracting with ethyl acetate The organic layer was washed with water by drying over anhydrous magnesium sulfate concentrating under reduced pressure The residue was purified with silica gel column chromatography (ethyl acetate:hexane=1:5 to 1:3)