methyl 4-(4-aminophenyl)butanoate

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: To a solution of 40 (500 mg, 2.59 mmol) in CH2Cl2 at room temperature were added Et3N (901 μL, 6.48 mmol) followed by benzenesulfonyl chloride (661 μL, 5.18 mmol). The mixture was stirred overnight at room temperature then treated with a saturated aqueous solution of NH4Cl. The phases were separated and the organic layer was extracted several times with CH2Cl2. The combined organic extracts were dried over (MgSO4) then evaporated under reduced pressure. The residue was dissolved in a solvent mixture of THF (25 mL) and water (25 mL) then LiOH (1.08 g, 25.9 mmol) was added. The mixture was heated at 50° C. for 1 h then treated with HCl (1N) until pH2. The phases were separated and the aqueous layer was extracted several times with AcOEt. The combined organic extracts were dried over (MgSO4) then evaporated. The crude was purified by flash chromatography using CH2Cl2/MeOH (95:5) as solvent mixture yielding 41 (800 mg, 96%) as a white solid The phases were separated the organic layer was extracted several times with CH2Cl2 The combined organic extracts were dried over (MgSO4) then evaporated under reduced pressure The residue was dissolved in a solvent mixture of THF (25 mL) and water (25 mL) The mixture was heated at 50° C. for 1 h The phases were separated the aqueous layer was extracted several times with AcOEt The combined organic extracts were dried over (MgSO4) then evaporated The crude was purified by flash chromatography

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

Procedure: To a solution of 40 (500 mg, 2.59 mmol) in CH2Cl2 at room temperature were added Et3N (901 μL, 6.48 mmol) followed by benzenesulfonyl chloride (661 μL, 5.18 mmol). The mixture was stirred overnight at room temperature then treated with a saturated aqueous solution of NH4Cl. The phases were separated and the organic layer was extracted several times with CH2Cl2. The combined organic extracts were dried over (MgSO4) then evaporated under reduced pressure. The residue was dissolved in a solvent mixture of THF (25 mL) and water (25 mL) then LiOH (1.08 g, 25.9 mmol) was added. The mixture was heated at 50° C. for 1 h then treated with HCl (1N) until pH2. The phases were separated and the aqueous layer was extracted several times with AcOEt. The combined organic extracts were dried over (MgSO4) then evaporated. The crude was purified by flash chromatography using CH2Cl2/MeOH (95:5) as solvent mixture yielding 41 (800 mg, 96%) as a white solid The phases were separated the organic layer was extracted several times with CH2Cl2 The combined organic extracts were dried over (MgSO4) then evaporated under reduced pressure The residue was dissolved in a solvent mixture of THF (25 mL) and water (25 mL) The mixture was heated at 50° C. for 1 h The phases were separated the aqueous layer was extracted several times with AcOEt The combined organic extracts were dried over (MgSO4) then evaporated The crude was purified by flash chromatography

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(4-aminophenyl)-butyric acid (5 g, 27.90 mmol) in MeOH (100 mL) at room temperature was added HCl conc. (37% 15 mL). The resulting mixture was stirred overnight at 50° C. then treated with a saturated aqueous solution NaHCO3 and Na2CO3 solid until pH 9. The solvent was evaporated under reduced pressure then the aqueous phase was extracted several times with CH2Cl2. The crude material was purified by flash chromatography using CH2Cl2/MeOH as solvent mixture yielding 40 (4.93 g, 91%) as orange solid. The solvent was evaporated under reduced pressure the aqueous phase was extracted several times with CH2Cl2 The crude material was purified by flash chromatography

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

Procedure: A mixture of methyl 4-(4-nitrophenyl)butanoate and methyl 4-(2-nitrophenyl)butanoate (2.24 g, 10.03 mmol) and 0.2 g of 10% Pd/C in 40 mL of methanol was vigorously stirred under hydrogen air. The mixture was stirred for 4 h at room temperature (monitored by TLC), and filtered through Celite. The solvent was evaporated. The residue was purified by chromatography to give the title compound (0.80 g, 41%): NMR (400 MHz in CDCl3, Bruker AVANCE-400): δ 1.89 (m, 2H, CH2), 2.31 (t, 2H, CH2—CH2—COOMe), 2.53 (t, 2H, CH2), 3.58 (br, 2H, NH2), 3.65 (s, 3H, OMe), 6.61 (d, 2H, J=3.5 Hz, Ar—H), 6.95 (d, 2H, J=3.4 Hz). The mixture was stirred for 4 h at room temperature (monitored by TLC) filtered through Celite The solvent was evaporated The residue was purified by chromatography

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

Procedure: A mixture of methyl 4-(4-nitrophenyl)butanoate and methyl 4-(2-nitrophenyl)butanoate (2.24 g, 10.03 mmol) and 0.2 g of 10% Pd/C in 40 mL of methanol was vigorously stirred under hydrogen air. The mixture was stirred for 4 h at room temperature (monitored by TLC), and filtered through Celite. The solvent was evaporated. The residue was purified by chromatography to give the title compound (0.80 g, 41%): NMR (400 MHz in CDCl3, Bruker AVANCE-400): δ 1.89 (m, 2H, CH2), 2.31 (t, 2H, CH2—CH2—COOMe), 2.53 (t, 2H, CH2), 3.58 (br, 2H, NH2), 3.65 (s, 3H, OMe), 6.61 (d, 2H, J=3.5 Hz, Ar—H), 6.95 (d, 2H, J=3.4 Hz). The mixture was stirred for 4 h at room temperature (monitored by TLC) filtered through Celite The solvent was evaporated The residue was purified by chromatography

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: To a solution of 40 (500 mg, 2.59 mmol) in CH2Cl2 at room temperature were added Et3N (901 μμL, 6.48 mmol) followed by benzenesulfonyl chloride (661 μL, 5.18 mmol). The mixture was stirred overnight at room temperature then treated with a saturated aqueous solution of NH4Cl. The phases were separated and the organic layer was extracted several times with CH2Cl2. The combined organic extracts were dried over (MgSO4) then evaporated under reduced pressure. The residue was dissolved in a solvent mixture of THF (25 mL) and water (25 mL) then LiOH (1.08 g, 25.9 mmol) was added. The mixture was heated at 50° C. for 1 h then treated with HCl (1N) until pH2. The phases were separated and the aqueous layer was extracted several times with AcOEt. The combined organic extracts were dried over (MgSO4) then evaporated. The crude was purified by flash chromatography using CH2Cl2/MeOH (95:5) as solvent mixture yielding 41 (800 mg, 96%) as a white solid The phases were separated the organic layer was extracted several times with CH2Cl2 The combined organic extracts were dried over (MgSO4) then evaporated under reduced pressure The residue was dissolved in a solvent mixture of THF (25 mL) and water (25 mL) The mixture was heated at 50° C. for 1 h The phases were separated the aqueous layer was extracted several times with AcOEt The combined organic extracts were dried over (MgSO4) then evaporated The crude was purified by flash chromatography

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-(4-aminophenyl)-butyric acid (5 g, 27.90 mmol) in MeOH (100 mL) at room temperature was added HCl conc. (37% 15 mL). The resulting mixture was stirred overnight at 50° C. then treated with a saturated aqueous solution NaHCO3 and Na2CO3 solid until pH 9. The solvent was evaporated under reduced pressure then the aqueous phase was extracted several times with CH2Cl2. The crude material was purified by flash chromatography using CH2Cl2/MeOH as solvent mixture yielding 40 (4.93 g, 91%) as orange solid. The solvent was evaporated under reduced pressure the aqueous phase was extracted several times with CH2Cl2 The crude material was purified by flash chromatography