(3-amino-4-chlorophenyl)methanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 100 mL flask was charged with (4-chloro-3-nitrophenyl)methanol (commercially available from Acros; 1.0 g, 5.5 mmol), ammonium formate (1.4 g, 22 mmol), and iron powder (1.2 g, 22 mmol). Toluene (15 mL) and water (15 mL) were added to the flask and the mixture was heated to reflux for 4 hours, after which time, the mixture was filtered through a plug of Celite. The supernatant was washed with ethyl acetate (3×50 ml). The combined organic solution was washed with water (100 ml), saturated sodium chloride solution (100 ml), dried over anhydrous sodium sulfate and filtered. The organic solvent was removed on a rotary evaporator under reduced pressure to yield (3-amino-4-chlorophenyl)methanol (0.74 g, 85% yield). The material was used without further purification. 1H-NMR (400 MHz, CDCl3) δ 6.88 (d, 1H), 6.56 (d, 1H), 6.40 (s, 1H), 5.85 (bs, 2H), 5.39 (bs, 1H), 5.85 (bs, 1H), 4.79 (s, 2H): MS (EI): 158 (MH+). the mixture was heated to reflux for 4 hours after which time, the mixture was filtered through a plug of Celite The supernatant was washed with ethyl acetate (3×50 ml) The combined organic solution was washed with water (100 ml), saturated sodium chloride solution (100 ml) dried over anhydrous sodium sulfate filtered The organic solvent was removed on a rotary evaporator under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 100 mL flask was charged with (4-chloro-3-nitrophenyl)methanol (commercially available from Acros; 1.0 g, 5.5 mmol), ammonium formate (1.4 g, 22 mmol), and iron powder (1.2 g, 22 mmol). Toluene (15 mL) and water (15 mL) were added to the flask and the mixture was heated to reflux for 4 hours, after which time, the mixture was filtered through a plug of Celite. The supernatant was washed with ethyl acetate (3×50 ml). The combined organic solution was washed with water (100 ml), saturated sodium chloride solution (100 ml), dried over anhydrous sodium sulfate and filtered. The organic solvent was removed on a rotary evaporator under reduced pressure to yield (3-amino-4-chlorophenyl)methanol (0.74 g, 85% yield). The material was used without further purification. 1H-NMR (400 MHz, CDCl3) δ 6.88 (d, 1H), 6.56 (d, 1H), 6.40 (s, 1H), 5.85 (bs, 2H), 5.39 (bs, 1H), 5.85 (bs, 1H), 4.79 (s, 2H): MS (EI): 158 (MH+). the mixture was heated to reflux for 4 hours after which time, the mixture was filtered through a plug of Celite The supernatant was washed with ethyl acetate (3×50 ml) The combined organic solution was washed with water (100 ml), saturated sodium chloride solution (100 ml) dried over anhydrous sodium sulfate filtered The organic solvent was removed on a rotary evaporator under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 100 mL flask was charged with (4-chloro-3-nitrophenyl)methanol (commercially available from Acros; 1.0 g, 5.5 mmol), ammonium formate (1.4 g, 22 mmol), and iron powder (1.2 g, 22 mmol). Toluene (15 mL) and water (15 mL) were added to the flask and the mixture was heated to reflux for 4 hours, after which time, the mixture was filtered through a plug of Celite. The supernatant was washed with ethyl acetate (3×50 ml). The combined organic solution was washed with water (100 ml), saturated sodium chloride solution (100 ml), dried over anhydrous sodium sulfate and filtered. The organic solvent was removed on a rotary evaporator under reduced pressure to yield (3-amino-4-chlorophenyl)methanol (0.74 g, 85% yield). The material was used without further purification. 1H-NMR (400 MHz, CDCl3) δ 6.88 (d, 1H), 6.56 (d, 1H), 6.40 (s, 1H), 5.85 (bs, 2H), 5.39 (bs, 1H), 5.85 (bs, 1H), 4.79 (s, 2H): MS (EI): 158 (MH+). the mixture was heated to reflux for 4 hours after which time, the mixture was filtered through a plug of Celite The supernatant was washed with ethyl acetate (3×50 ml) The combined organic solution was washed with water (100 ml), saturated sodium chloride solution (100 ml) dried over anhydrous sodium sulfate filtered The organic solvent was removed on a rotary evaporator under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 3-amino-4-chloro-benzyl alcohol (8.0 g, 51.0 mmol) and 4-hydroxy-6-methyl-2-pyrone (6.4 g, 51.0 mmol) were taken up in 1,2-dichlorobenzene (50 ml). The mixture was plunged into a 165° C. oil bath where it stirred for 20 minutes. The reaction was cooled to room temperature and the reaction was worked up by washing with saturated NaHCO3 (aq.) and extracting impurities with ethyl acetate. The product remained in the aqueous layer. The basic aqueous layer was made acidic with concentrated HCl. The product was extracted from the acidic aqueous layer with ethyl acetate. The ethyl acetate layer was dried over Na2SO4 and the solvent removed in vacuo. The product was obtained as a yellow oil in a 26% yield and was carried through to the next step with no further purification. 1H NMR (300 MHz, CD3OD) δ 7.62 (d, J=8.26 Hz, 2H), 7.51 (dd, J=8.46, 2.22 Hz, 1H), 7.36 (d, J=2.01 Hz, 1H), 6.13 (br s, 1H), 5.84 (d, J=2.42 Hz, 1H), 4.68 (s, 2H), 1.97 (s, 3H); LC/MS, tr=0.25 minutes and 1.41 minutes (tautomer), (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 266 (M+H). was plunged into a 165° C. by washing with saturated NaHCO3 (aq.) extracting impurities with ethyl acetate The product was extracted from the acidic aqueous layer with ethyl acetate The ethyl acetate layer was dried over Na2SO4 the solvent removed in vacuo The product was obtained as a yellow oil in a 26% yield was carried through to the next step with no further purification LC/MS, tr=0.25 minutes and 1.41 minutes (tautomer), (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-[2-chloro-5-(hydroxymethyl)phenyl]-4-hydroxy-6-methylpyridin-2(1H)-one (from step 2) (3.5 g, 13.2 mmol) was taken up in DMF (10 ml) and cooled to 0° C. 2,4-Difluorobenzyl bromide (1.7 ml, 13.2 mmol) and K2CO3 (1.8 g, 13.2 mmol) were added and the reaction stirred for 6 hours. The reaction was worked up by adding saturated NaHCO3 (aq.) and extracting with ethyl acetate. The ethyl acetate extraction was washed with water, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and dried over Na2SO4, filtered, and the solvent removed in vacuo. The product was obtained in 83% crude yield and carried through to the next step as a brown oil. LC/MS, tr=2.48 minutes (5 to 95% acetonitrile/water over 5 minutes at 1 ml/min with detection 254 nm, at 50° C.). ES-MS m/z 392 (M+H). ES-HRMS m/z 392.0853 (M+H calcd for C20H17ClF2NO3 requires 392.0860). extracting with ethyl acetate The ethyl acetate extraction was washed with water the aqueous layer was extracted with ethyl acetate dried over Na2SO4 filtered the solvent removed in vacuo The product was obtained in 83% crude yield

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of (3-amino-4-chloro-phenyl)-methanol (2.0 g, 12.7 mmol) in pyridine (26 mL) was treated with 3,4-dimethoxybenzenesulfonyl chloride (3.3 g, 1.1 eq). The solution was stirred at RT overnight. The mixture was then partitioned between EA and 3M HCl. The organic layer was washed with brine, dried over MgSO4 and concentrated. The product was recovered as a brownish foam. The mixture was then partitioned between EA and 3M HCl The organic layer was washed with brine dried over MgSO4 concentrated The product was recovered as a brownish foam

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (4-chloro-3-nitro-phenyl)-methanol (4.96 g, 26.4 mmol) in MeOH (60 mL) and conc HCl (22 ml) was added iron powder (4.43 g, 3 eq) in portions. The mixture was then heated at reflux (65° C.) for 6 h, cooled and poured on ice water. The solution was neutralised with dilute NaOH and filtered. The filtrate was extracted with EA several times. The combined organic layers were washed with brine, dried over MgSO4 and concentrated. The product was recovered as a greyish solid (3.8 g, 92%). The mixture was then heated cooled poured on ice water filtered The filtrate was extracted with EA several times The combined organic layers were washed with brine dried over MgSO4 concentrated The product was recovered as a greyish solid (3.8 g, 92%)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 100 mL flask was charged with (4-chloro-3-nitrophenyl)methanol (commercially available from Acros; 1.0 g, 5.5 mmol), ammonium formate (1.4 g, 22 mmol), and iron powder (1.2 g, 22 mmol). Toluene (15 mL) and water (15 mL) were added to the flask and the mixture was heated to reflux for 4 hours, after which time, the mixture was filtered through a plug of Celite. The supernatant was washed with ethyl acetate (3×50 ml). The combined organic solution was washed with water (100 ml), saturated sodium chloride solution (100 ml), dried over anhydrous sodium sulfate and filtered. The organic solvent was removed on a rotary evaporator under reduced pressure to yield (3-amino-4-chlorophenyl)methanol (0.74 g, 85% yield). The material was used without further purification. 1H-NMR (400 MHz, CDCl3) δ 6.88 (d, 1H), 6.56 (d, 1H), 6.40 (s, 1H), 5.85 (bs, 2H), 5.39 (bs, 1H), 5.85 (bs, 1H), 4.79 (s, 2H): MS (EI): 158 (MH+). the mixture was heated to reflux for 4 hours after which time, the mixture was filtered through a plug of Celite The supernatant was washed with ethyl acetate (3×50 ml) The combined organic solution was washed with water (100 ml), saturated sodium chloride solution (100 ml) dried over anhydrous sodium sulfate filtered The organic solvent was removed on a rotary evaporator under reduced pressure