tert-butyl N-(4-chloro-3-hydroxyphenyl)carbamate

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

Procedure: To a cooled (0° C.) solution of 4-chloro-3-hydroxyphenylcarbamic acid tert-butyl ester (55 g, 0.23 mol), (S)-1-methyl-pyrrolidin-3-ol (24 g, 0.24 mol), and triphenylphosphine (89 g, 0.34 mol) in THF (1.1 L) was added dropwise via addition funnel a solution of DIAD (67 mL, 0.34 mol) in THF (100 mL) over 1 h. The resultant solution was allowed to slowly warm to ambient temperature and maintained for 16 h. The THF was removed in vacuo and the residue treated with 6 N HCl (650 mL). The resultant mixture was stirred at room temperature for 4 h, at which time it was diluted with water (500 mL) and the filtered to remove the triphenylphosphine oxide. The filtrate was washed with EtOAc (3×1 L) and chloroform (5×1 L) to remove additional reaction by-products. The aqueous layer was then basified with solid NaOH pellets and extracted with ether (2×1 L) and EtOAc (2×1 L). The combined organic layers were washed with saturated NaHCO3 (2×1 L) and brine (1 L), dried (MgSO4), and concentrated to give 40 g (80%) of the title compound: MS (ES+) m/e [M+H]+ 227. maintained for 16 h The THF was removed in vacuo the residue treated with 6 N HCl (650 mL) was diluted with water (500 mL) the filtered to remove the triphenylphosphine oxide The filtrate was washed with EtOAc (3×1 L) and chloroform (5×1 L) to remove additional reaction by-products extracted with ether (2×1 L) and EtOAc (2×1 L) The combined organic layers were washed with saturated NaHCO3 (2×1 L) and brine (1 L) dried (MgSO4) concentrated

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

Procedure: To a cooled (0° C.) solution of 4-chloro-3-hydroxyphenylcarbamic acid tert-butyl ester (55 g, 0.23 mol), (S)-1-methyl-pyrrolidin-3-ol (24 g, 0.24 mol), and triphenylphosphine (89 g, 0.34 mol) in THF (1.1 L) was added dropwise via addition funnel a solution of DIAD (67 mL, 0.34 mol) in THF (100 mL) over 1 h. The resultant solution was allowed to slowly warm to ambient temperature and maintained for 16 h. The THF was removed in vacuo and the residue treated with 6 N HCl (650 mL). The resultant mixture was stirred at room temperature for 4 h, at which time it was diluted with water (500 mL) and the filtered to remove the triphenylphosphine oxide. The filtrate was washed with EtOAc (3×1 L) and chloroform (5×1 L) to remove additional reaction by-products. The aqueous layer was then basified with solid NaOH pellets and extracted with ether (2×1 L) and EtOAc (2×1 L). The combined organic layers were washed with saturated NaHCO3 (2×1 L) and brine (1 L), dried (MgSO4), and concentrated to give 40 g (80%) of the title compound: MS (ES+) m/e [M+H]+ 227. maintained for 16 h The THF was removed in vacuo the residue treated with 6 N HCl (650 mL) was diluted with water (500 mL) the filtered to remove the triphenylphosphine oxide The filtrate was washed with EtOAc (3×1 L) and chloroform (5×1 L) to remove additional reaction by-products extracted with ether (2×1 L) and EtOAc (2×1 L) The combined organic layers were washed with saturated NaHCO3 (2×1 L) and brine (1 L) dried (MgSO4) concentrated

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

Procedure: To a cooled (0° C.) solution of 4-chloro-3-hydroxyphenylcarbamic acid tert-butyl ester (55 g, 0.23 mol), (S)-1-methyl-pyrrolidin-3-ol (24 g, 0.24 mol), and triphenylphosphine (89 g, 0.34 mol) in THF (1.1 L) was added dropwise via addition funnel a solution of DIAD (67 mL, 0.34 mol) in THF (100 mL) over 1 h. The resultant solution was allowed to slowly warm to ambient temperature and maintained for 16 h. The THF was removed in vacuo and the residue treated with 6 N HCl (650 mL). The resultant mixture was stirred at room temperature for 4 h, at which time it was diluted with water (500 mL) and the filtered to remove the triphenylphosphine oxide. The filtrate was washed with EtOAc (3×1 L) and chloroform (5×1 L) to remove additional reaction by-products. The aqueous layer was then basified with solid NaOH pellets and extracted with ether (2×1 L) and EtOAc (2×1 L). The combined organic layers were washed with saturated NaHCO3 (2×1 L) and brine (1 L), dried (MgSO4), and concentrated to give 40 g (80%) of the title compound: MS (ES+) m/e [M+H]+227. maintained for 16 h The THF was removed in vacuo the residue treated with 6 N HCl (650 mL) was diluted with water (500 mL) the filtered to remove the triphenylphosphine oxide The filtrate was washed with EtOAc (3×1 L) and chloroform (5×1 L) to remove additional reaction by-products extracted with ether (2×1 L) and EtOAc (2×1 L) The combined organic layers were washed with saturated NaHCO3 (2×1 L) and brine (1 L) dried (MgSO4) concentrated

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

Procedure: To a cooled (0° C.) solution of 4-chloro-3-hydroxyphenylcarbamic acid tert-butyl ester (55 g, 0.23 mol), (S)-1-methyl-pyrrolidin-3-ol (24 g, 0.24 mol), and triphenylphosphine (89 g, 0.34 mol) in THF (1.1 L) was added dropwise via addition funnel a solution of DIAD (67 mL, 0.34 mol) in THF (100 mL) over 1 h. The resultant solution was allowed to slowly warm to ambient temperature and maintained for 16 h. The THF was removed in vacuo and the residue treated with 6 N HCl (650 mL). The resultant mixture was stirred at room temperature for 4 h, at which time it was diluted with water (500 mL) and the filtered to remove the triphenylphosphine oxide. The filtrate was washed with EtOAc (3×1 L) and chloroform (5×1 L) to remove additional reaction by-products. The aqueous layer was then basified with solid NaOH pellets and extracted with ether (2×1 L) and EtOAc (2×1 L). The combined organic layers were washed with saturated NaHCO3 (2×1 L) and brine (1 L), dried (MgSO4), and concentrated to give 40 g (80%) of the title compound: MS (ES+) m/e [M+H]+ 227. maintained for 16 h The THF was removed in vacuo the residue treated with 6 N HCl (650 mL) was diluted with water (500 mL) the filtered to remove the triphenylphosphine oxide The filtrate was washed with EtOAc (3×1 L) and chloroform (5×1 L) to remove additional reaction by-products extracted with ether (2×1 L) and EtOAc (2×1 L) The combined organic layers were washed with saturated NaHCO3 (2×1 L) and brine (1 L) dried (MgSO4) concentrated