methyl 4-amino-3-hydroxybenzoate

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: Using methyl 4-amino-3-hydroxybenzoate (2 g, 12 mmol), triethylamine (2.17 mL, 16 mmol) and chloroacetyl chloride (1.13 mL, 13 mmol) in THF (70 mL) followed by sodium hydride (1.0 g of a 60% suspension in oil, 24 mmol) to yield the title compound as a brown solid (2.33 g, 94%). δH (DMSO-d6) 3.81 (3H, s), 4.65 (2H, s), 6.99 (1H, d, J 8.3 Hz), 7.43 (1H, d, J 1.5 Hz). 7.59 (1H, dd, J 8.5, 1.9 Hz), 11.10 (1H, br s). LCMS (ES+) 208 (M+H)+.

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

Procedure: To a stirred solution of methyl 4-amino-3-hydroxybenzoate (4.45 g, 26.6 mmol) in THF (250 ml) at room temperature, thiophosgene (2.4 mL, 32 mmol) was added slowly via a syringe pump over a period of 1 hr. After stirring for 4 hr, excess thiophosgene was quenched by addition of a saturated aqueous solution of NH4Cl (100 mL), and the THF was removed by evaporation under reduced pressure. More water was added, and the aqueous mixture was extracted with EtOAc (3×). The Combined organic phase was washed with brine, dried (MgSO4), concentrated in vacuo to give Compound 4 as a tan solid. LC-MS, M+1=210 excess thiophosgene was quenched by addition of a saturated aqueous solution of NH4Cl (100 mL) the THF was removed by evaporation under reduced pressure More water was added the aqueous mixture was extracted with EtOAc (3×) The Combined organic phase was washed with brine dried (MgSO4) concentrated in vacuo

Conditions: temp:210.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 4-amino-3-hydroxy-benzoate 25a (0.3 g, 1.8 mmol) and benzoyl chloride 25b (0.23 mL, 2.0 mmol) in dioxane (2.5 mL) was heated at 210° C. under microwave for 15 min. The reaction mixture was diluted with CH2Cl2 and washed with aq. NaHCO3. The organic solution was dried over Na2SO4, concentrated and purified by flash column chromatography (silica gel, 20% EtOAc/heptane) to give 25c (0.39 g). washed with aq. NaHCO3 The organic solution was dried over Na2SO4 concentrated purified by flash column chromatography (silica gel, 20% EtOAc/heptane)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 4-amino-3-hydroxybenzoate (1 eq.) in THF was diluted with aqueous HCl 3N and cooled to 0° C. Sodium nitrite (1.1 eq.) in H2O was added over 5 min. The reaction mixture was stirred for 25 min at 0° C. and then a solution of potassium iodide (4 eq.) in H2O was added in one portion, and stirred for 15 min. The reaction mixture was partitioned between water and EtOAc, the organic layer was washed with saturated aqueous NaCl, dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with DCM) to afford methyl 3-hydroxy-4-iodobenzoate. stirred for 15 min The reaction mixture was partitioned between water and EtOAc the organic layer was washed with saturated aqueous NaCl dried over MgSO4 filtered concentrated under reduced pressure The crude was purified by chromatography on silica gel (elution with DCM)

Conditions: temp:210.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 4-amino-3-hydroxy-benzoate 1s (0.3 g, 1.8 mmol) and benzoyl chloride 1t (0.23 mL, 2.0 mmol) in dioxane (2.5 mL) was heated at 210° C. under microwave for 15 min. The reaction mixture was diluted with CH2Cl2 and washed with aq. NaHCO3. The organic solution was dried over Na2SO4, concentrated and purified by flash column chromatography (silica gel, 20% EtOAc/heptane) to give 1u (0.39 g). washed with aq. NaHCO3 The organic solution was dried over Na2SO4 concentrated purified by flash column chromatography (silica gel, 20% EtOAc/heptane)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: HCl (g) was bubbled through a solution of 4-amino-3-hydroxybenzoic acid (7 g, 54.8 mmol) in MeOH (450 mL) until saturated then the mixture was heated at 70° C. for 16 hr. The mixture was concentrated in vacuo, the residue taken up in EtOAc, washed with saturated NaHCO3 then brine and dried (MgSO4). Removal of the solvent yielded the title compound as a brown solid. The mixture was concentrated in vacuo washed with saturated NaHCO3 brine and dried (MgSO4) Removal of the solvent

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

Procedure: The urea was prepared from 2-hydroxy 4-carbomethoxy aniline (0.167 g, 1 mmol) and 2-phenyl phenyl isocyanate (1 mmol) by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane. Filtering afforded the desired compound (0.185 g, 50%). EI-MS m/z 363 (M−H)− It was purified by dilution with methylene chloride and precipitation with hexane Filtering

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

Procedure: The urea was prepared from 2-hydroxy 4-carbomethoxy aniline (0.167 g, 1 mmol) and 2-bromo phenyl isocyanate (1 mmol) by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane. Filtering afforded the desired compound (0.12 g, 33%). EI-MS m/z 363 (M−H)− It was purified by dilution with methylene chloride and precipitation with hexane Filtering