2-(aminomethyl)-4-chlorophenol

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

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

Procedure: A mixture of 2-hydroxy-5-chlorobenzylamine (1.22 g, 4.77 mmol assuming the bisulfate salt), (BOC)2O (1.56 g, 7.16 mmol) and N-methylmorpholine (1.05 ml, 9.54 mmol) in DMF (10 ml) was stirred for 5 h at r.t. The reaction was partitioned between water and ethyl acetate and the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine, dried (Na2SO4) and evaporated in vacuo to a solid. The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml) to give the title compound: The reaction was partitioned between water and ethyl acetate the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine dried (Na2SO4) evaporated in vacuo to a solid The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml)

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

Procedure: A mixture of 2-hydroxy-5-chlorobenzylamine (1.22 g, 4.77 mmol assuming the bisulfate salt), (BOC)2O (1.56 g, 7.16 mmol) and N-methylmorpholine (1.05 ml, 9.54 mmol) in DMF (10 ml) was stirred for 5 h at r.t. The reaction was partitioned between water and ethyl acetate and the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine, dried (Na2SO4) and evaporated in vacuo to a solid. The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml) to give the title compound: The reaction was partitioned between water and ethyl acetate the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine dried (Na2SO4) evaporated in vacuo to a solid The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml)

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

Procedure: A mixture of 2-hydroxy-5-chlorobenzylamine (1.22 g, 4.77 mmol assuming the bisulfate salt), (BOC)2O (1.56 g, 7.16 mmol) and N-methylmorpholine (1.05 ml, 9.54 mmol) in DMF (10 ml) was stirred for 5 h at r.t. The reaction was partitioned between water and ethyl acetate and the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine, dried (Na2SO4) and evaporated in vacuo to a solid. The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml) to give the title compound: The reaction was partitioned between water and ethyl acetate the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine dried (Na2SO4) evaporated in vacuo to a solid The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml)

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

Procedure: A mixture of 2-hydroxy-5-chlorobenzylamine (1.22 g, 4.77 mmol assuming the bisulfate salt), (BOC)2O (1.56 g, 7.16 mmol) and N-methylmorpholine (1.05 ml, 9.54 mmol) in DMF (10 ml) was stirred for 5 h at r.t. The reaction was partitioned between water and ethyl acetate and the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine, dried (Na2SO4) and evaporated in vacuo to a solid. The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml) to give the title compound: The reaction was partitioned between water and ethyl acetate the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine dried (Na2SO4) evaporated in vacuo to a solid The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml)

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

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

Procedure: To a suspension of LiAlH4 (437 mg, 11.5 mmol) in dry tetrahydrofuran (30 mL) under nitrogen atmosphere, a solution of 5-chloro-2-hydroxybenzamide 74 (1.5 g, 5.7 mmol) in THF (10 mL) was added and the mixture was refluxed for 3 h. After cooling, the excess of LiAlH4 was destroyed with a saturated solution of sodium sulfate. The mixture was filtered on MgSO4 and the filtrate concentrated in vacuo. The residue was partitioned between water (30 mL) and CH2Cl2 (30 mL). The aqueous phase was separated and extracted with CH2Cl2 (20 mL×2). The combined organic phases were dried over Na2SO4, filtered and concentrated. The obtained solid was recrystallized from ethanol obtaining 787 mg of pure product (yield 88%). 1H NMR (CDCl3, 300 MHz) δ 7.10 (dd, J=6.6, 2.7 Hz, 1H), 6.94 (d, J=2.4 Hz, 1H), 6.76 (d, J=8.7 Hz, 1H), 4.10 (br s, 2H), 1.61 (br s, 2H). MS (m/e) (API-ES) 158 (M+H)+, m.p. 160-162° C. the mixture was refluxed for 3 h After cooling the excess of LiAlH4 was destroyed with a saturated solution of sodium sulfate The mixture was filtered on MgSO4 the filtrate concentrated in vacuo The residue was partitioned between water (30 mL) and CH2Cl2 (30 mL) The aqueous phase was separated extracted with CH2Cl2 (20 mL×2) The combined organic phases were dried over Na2SO4 filtered concentrated

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

Procedure: A mixture of 2-hydroxy-5-chlorobenzylamine (1.22 g, 4.77 mmol assuming the bisulfate salt), (BOC)2O (1.56 g, 7.16 mmol) and N-methylmorpholine (1.05 ml, 9.54 mmol) in DMF (10 ml) was stirred for 5 h at r.t. The reaction was partitioned between water and ethyl acetate and the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine, dried (Na2SO4) and evaporated in vacuo to a solid. The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml) to give the title compound: The reaction was partitioned between water and ethyl acetate the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine dried (Na2SO4) evaporated in vacuo to a solid The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml)

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

Procedure: A mixture of 2-hydroxy-5-chlorobenzylamine (1.22 g, 4.77 mmol assuming the bisulfate salt), (BOC)2O (1.56 g, 7.16 mmol) and N-methylmorpholine (1.05 ml, 9.54 mmol) in DMF (10 ml) was stirred for 5 h at r.t. The reaction was partitioned between water and ethyl acetate and the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine, dried (Na2SO4) and evaporated in vacuo to a solid. The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml) to give the title compound: The reaction was partitioned between water and ethyl acetate the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine dried (Na2SO4) evaporated in vacuo to a solid The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml)

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

Procedure: A mixture of 2-hydroxy-5-chlorobenzylamine (1.22 g, 4.77 mmol assuming the bisulfate salt), (BOC)2O (1.56 g, 7.16 mmol) and N-methylmorpholine (1.05 ml, 9.54 mmol) in DMF (10 ml) was stirred for 5 h at r.t. The reaction was partitioned between water and ethyl acetate and the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine, dried (Na2SO4) and evaporated in vacuo to a solid. The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml) to give the title compound: The reaction was partitioned between water and ethyl acetate the organic layer was washed with 5% KHSO4 solution (2 times), sodium hydrogen carbonate solution and brine dried (Na2SO4) evaporated in vacuo to a solid The crude product was recrystallized from ethyl acetate/hexanes (1:5, 12 ml)