2-amino-5-bromo-4-chlorophenol

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-5-bromo-4-chlorophenol (53) (4.746 g, 21.1 mmol), trifluoromethanesulfonic acid Ytterbium (III) salt (130 mg, 1% mol) and trimethyl orthoformate (4.03 ml, 1.5 eq.) in 15 ml EtOH was heated at 90° C. for 1 h. After cooling down to r.t. Crystalline formed was filtered, washed with MeOH, dried to give 4.694 g 54 as pale brown fine needles (yield: 90.3%) After cooling down to r.t Crystalline formed was filtered washed with MeOH dried

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

実験手順: To a suspension of 4-bromo-3-chloro-6-methoxyaniline (52) (5 g, 21.1 mmol) in 50 ml DCM was added 1 M BBr3 in DCM (43 ml, 43 mmol) at 0° C. The reaction mixture was stirred at r.t. for 3 h, which turned to a light brown solution and back to a light brown suspension. After quenched with aq. sodium bicarbonate solution, the mixture was extracted with EA. The org. phase was washed with brine, dried over sodium sulfate, concentrated to dryness to give 4.746 g 53 as light brown solid. Yield: 100%, purity>95%. After quenched with aq. sodium bicarbonate solution the mixture was extracted with EA phase was washed with brine dried over sodium sulfate concentrated to dryness

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-5-bromo-4-chlorophenol (29) (865 mg, 3.89 mmol), trifluoromethanesulfonic acid Ytterbium (III) salt (24 mg, 1% mol) and trimethyl orthoacetate (610 μl, 1.2 eq.) in 3 ml EtOH was heated at 90° C. for 1 h. After cooling down to r.t., off-white needles fell off, which were filtered, washed with MeOH, water and dried to give 791 mg title compound as off-white crystalline solid. Yield: 80.2%; purity>95%. After cooling down to r.t. which were filtered washed with MeOH, water dried

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

実験手順: A mixture of 2-amino-5-bromo-4-chlorophenol (29). (865 mg, 3.89 mmol), trifluoromethanesulfonic acid Ytterbium (III) salt (24 mg, 1% mol) and trimethyl orthoformate (511 μl, 1.2 eq.) in 2 ml EtOH was heated at 90° C. for 2 h. After cooling down to r.t., the reaction mixture was taken up in EA, washed with aq. NaHCO3 and brine, dried over Na2SO4, concentrated to dryness. The resulting brown solid was dissolved in DCM and subjected to silica gel column purification using 0-100% B (A: hexane; B: 50% EA in hexane) to furnish 590 mg 30 as yellow solid (yield: 65.2%). washed with aq. NaHCO3 and brine dried over Na2SO4 concentrated to dryness The resulting brown solid was dissolved in DCM subjected to silica gel column purification

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

実験手順: A mixture of 2-amino-5-bromo-4-chlorophenol (29). (865 mg, 3.89 mmol), trifluoromethanesulfonic acid Ytterbium (III) salt (24 mg, 1% mol) and trimethyl orthoformate (511 μl, 1.2 eq.) in 2 ml EtOH was heated at 90° C. for 2 h. After cooling down to r.t., the reaction mixture was taken up in EA, washed with aq. NaHCO3 and brine, dried over Na2SO4, concentrated to dryness. The resulting brown solid was dissolved in DCM and subjected to silica gel column purification using 0-100% B (A: hexane; B: 50% EA in hexane) to furnish 590 mg 30 as yellow solid (yield: 65.2%). washed with aq. NaHCO3 and brine dried over Na2SO4 concentrated to dryness The resulting brown solid was dissolved in DCM subjected to silica gel column purification

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

実験手順: To a suspension of 4-bromo-3-chloro-6-methoxyaniline (28) (944 mg, 4 mmol) in 10 ml DCM was added 1 M BBr3 in DCM (8 ml, 8 mmol). The reaction mixture was stirred at r.t. for 2 h, which turned to a brown solution and back to a brown suspension. After quenched with aq. sodium bicarbonate solution, the mixture was extracted with EA. The org. phase was washed with brine, dried over sodium sulfate, concentrated to dryness to give 865 mg of 29 as a brown solid. Yield: 97.2%, purity>95%. After quenched with aq. sodium bicarbonate solution the mixture was extracted with EA phase was washed with brine dried over sodium sulfate concentrated to dryness

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-5-bromo-4-chlorophenol (29) (865 mg, 3.89 mmol), trifluoromethanesulfonic acid Ytterbium (III) salt (24 mg, 1% mol) and trimethyl orthoacetate (610 μl, 1.2 eq.) in 3 ml EtOH was heated at 90° C. for 1 h. After cooling down to r.t., off-white needles fell off, which were filtered, washed with MeOH, water and dried to give 791 mg title compound as off-white crystalline solid. Yield: 80.2%; purity>95%. After cooling down to r.t. which were filtered washed with MeOH, water dried

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-5-bromo-4-chlorophenol (29) (865 mg, 3.89 mmol), trifluoromethanesulfonic acid Ytterbium (III) salt (24 mg, 1% mol) and trimethyl orthoformate (511 μl, 1.2 eq.) in 2 ml EtOH was heated at 90° C. for 2 h. After cooling down to r.t., the reaction mixture was taken up in EA, washed with aq. NaHCO3 and brine, dried over Na2SO4, concentrated to dryness. The resulting brown solid was dissolved in DCM and subjected to silica gel column purification using 0-100% B (A: hexane; B: 50% EA in hexane) to furnish 590 mg 30 as yellow solid (yield: 65.2%). After cooling down to r.t. washed with aq. NaHCO3 and brine dried over Na2SO4 concentrated to dryness The resulting brown solid was dissolved in DCM subjected to silica gel column purification

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

実験手順: To a suspension of 4-bromo-3-chloro-6-methoxyaniline (28) (944 mg, 4 mmol) in 10 ml DCM was added 1 M BBr3 in DCM (8 ml, 8 mmol). The reaction mixture was stirred at r.t. for 2 h, which turned to a brown solution and back to a brown suspension. After quenched with aq. sodium bicarbonate solution, the mixture was extracted with EA. The org. phase was washed with brine, dried over sodium sulfate, concentrated to dryness to give 865 mg of 29 as a brown solid. Yield: 97.2%, purity>95%. After quenched with aq. sodium bicarbonate solution the mixture was extracted with EA phase was washed with brine dried over sodium sulfate concentrated to dryness

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

実験手順: To a suspension of 4-bromo-3-chloro-6-methoxyaniline (28) (944 mg, 4 mmol) in 10 ml DCM was added 1 M BBr3 in DCM (8 ml, 8 mmol). The reaction mixture was stirred at r.t. for 2 h, which turned to a brown solution and back to a brown suspension. After quenched with aq. sodium bicarbonate solution, the mixture was extracted with EA. The org. phase was washed with brine, dried over sodium sulfate, concentrated to dryness to give 865 mg of 29 as a brown solid. Yield: 97.2%, purity>95%. After quenched with aq. sodium bicarbonate solution the mixture was extracted with EA phase was washed with brine dried over sodium sulfate concentrated to dryness

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-5-bromo-4-chlorophenol (53) (4.746 g, 21.1 mmol), trifluoromethanesulfonic acid Ytterbium (III) salt (130 mg, 1% mol) and trimethyl orthoformate (4.03 ml, 1.5 eq.) in 15 ml EtOH was heated at 90° C. for 1 h. After cooling down to r.t. Crystalline formed was filtered, washed with MeOH, dried to give 4.694 g 54 as pale brown fine needles (yield: 90.3%) After cooling down to r.t Crystalline formed was filtered washed with MeOH dried

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

実験手順: To a suspension of 4-bromo-3-chloro-6-methoxyaniline (52) (5 g, 21.1 mmol) in 50 ml DCM was added 1 M BBr3 in DCM (43 ml, 43 mmol) at 0° C. The reaction mixture was stirred at r.t. for 3 h, which turned to a light brown solution and back to a light brown suspension. After quenched with aq. sodium bicarbonate solution, the mixture was extracted with EA. The org. phase was washed with brine, dried over sodium sulfate, concentrated to dryness to give 4.746 g 53 as light brown solid. Yield: 100%, purity>95%. After quenched with aq. sodium bicarbonate solution the mixture was extracted with EA phase was washed with brine dried over sodium sulfate concentrated to dryness