tert-butyl N-[3-(hydroxymethyl)phenyl]carbamate

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: The (3-hydroxymethyl-phenyl)-carbamic acid tert-butyl ester (1.67 g, 7.49 mmol) and triphenylphosphine (2.61 g, 9.96 mmol) were combined and dissolved in tetrahydrofuran (40 mL). Carbon tetrabromide (3.23 g, 9.74 mmol) was dissolved in acetonitrile (20 mL) and added dropwise to the reaction while stirring. After stirring for 5 h, the reaction was concentrated in vacuo to give a thick golden oil. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 20% ethyl acetate/hexanes) afforded (3-bromomethyl-phenyl)-carbamic acid tert-butyl ester (1.52 g, 78%) as a white powder: H1-NMR (400 MHz, CDCl3) δ 1.53 (9H, s), 4.46 (2H, s), 6.47 (1H, bs), 7.06 (1H, d, J=7.2 Hz), 7.19-7.27 (2H, m), 7.51 (1H, s). added dropwise to the reaction After stirring for 5 h the reaction was concentrated in vacuo to give a thick golden oil Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 20% ethyl acetate/hexanes)

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

Procedure: The (3-hydroxymethyl-phenyl)-carbamic acid tert-butyl ester (1.67 g, 7.49 mmol) and triphenylphosphine (2.61 g, 9.96 mmol) were combined and dissolved in tetrahydrofuran (40 mL). Carbon tetrabromide (3.23 g, 9.74 mmol) was dissolved in acetonitrile (20 mL) and added dropwise to the reaction while stirring. After stirring for 5 h, the reaction was concentrated in vacuo to give a thick golden oil. Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 20% ethyl acetate/hexanes) afforded (3-bromomethyl-phenyl)-carbamic acid tert-butyl ester (1.52 g, 78%) as a white powder: H1-NMR (400 MHz, CDCl3) δ 1.53 (9H, s), 4.46 (2H, s), 6.47 (1H, bs), 7.06 (1H, d, J=7.2 Hz), 7.19-7.27 (2H, m), 7.51 (1H, s). added dropwise to the reaction After stirring for 5 h the reaction was concentrated in vacuo to give a thick golden oil Purification by flash column chromatography (Merck silica gel 60, 40-63 μm; 20% ethyl acetate/hexanes)

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of tert-butyl [3-(hydroxymethyl)phenyl]carbamate (0.6 g, 2.7 mmol) [J. Med. Chem. 1989, 32, 807-826] in dichloromethane (8.4 mL) at −10° C. was treated with N,N-diisopropylethylamine (0.7 mL, 4.0 mmol) followed by methanesulfonyl chloride (0.31 mL, 4.0 mmol and stirred at −10° C. for 1 h. The reaction mixture was quenched with water (50 mL) and extracted with dichloromethane (100 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and evaporated to give the desired product as a crude yellow oil that was used without further purification. LCMS for C13H19NO5SNa (M+Na)+: m/z=323.9. The reaction mixture was quenched with water (50 mL) extracted with dichloromethane (100 mL) The organic layer was separated dried over anhydrous sodium sulfate filtered evaporated

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of tert-butyl [3-(hydroxymethyl)phenyl]carbamate (0.6 g, 2.7 mmol) [J. Med. Chem. 1989, 32, 807-826] in dichloromethane (8.4 mL) at −10° C. was treated with N,N-diisopropylethylamine (0.7 mL, 4.0 mmol) followed by methanesulfonyl chloride (0.31 mL, 4.0 mmol and stirred at −10° C. for 1 h. The reaction mixture was quenched with water (50 mL) and extracted with dichloromethane (100 mL). The organic layer was separated, dried over anhydrous sodium sulfate, filtered, and evaporated to give the desired product as a crude yellow oil that was used without further purification. LCMS for C13H19NO5SNa (M+Na)+: m/z=323.9. The reaction mixture was quenched with water (50 mL) extracted with dichloromethane (100 mL) The organic layer was separated dried over anhydrous sodium sulfate filtered evaporated

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

Procedure: 2-(2-(4-(4-Hydroxyphenoxy)phenyl)acetylamino)benzoic acid methyl ester obtained by the Reference Example 24 (315 mg, 0.83 mmol) was dissolved in 20 ml of methylene chloride-THF mixture (1:1 v/v), added with 3-(tert-butoxycarbonylamino)benzyl alcohol (465 mg, 2.1 mmol), 1,1′-azobis(N,N′-dimethylformamide) (359 mg, 2.08 mmol) and tri-n-butyl phosphine (520 ml, 2.1 mmol) and the reaction mixture was stirred over a night. After completing the reaction, the solvent was removed under reduced pressure and the obtained crude residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate 75:25 v/v) to obtain the subject compound (404 mg, 0.693 mmol) in the form of a colorless gummy substance. The result of 1H-NMR was consistent with the above structure. the reaction the solvent was removed under reduced pressure the obtained crude residue was purified by silica gel chromatography (elution solvent; hexane:ethyl acetate 75:25 v/v)

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

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

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