tert-butyl N-(2-phenylmethoxyethyl)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:; See reaction.notes.procedure_details.

Procedure: Benzyltrimethylammonium chloride (4.61 g, 24.8 mmol) was added to a mixture of tert-butyl 2-hydroxyethylcarbamate (40.0 g, 248 mmol), dichloromethane (600 mL), and 50% aqueous sodium hydroxide (400 mL). Benzyl bromide (29.5 mL, 248 mmol) was then added, and the reaction was stirred for three hours. Ice water was added (1 L), and the aqueous solution was extracted with chloroform (5×). The combined organic solutions were washed with water (2×) and brine (3×), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Upon concentration, a white precipitate formed, and the organic solution was washed again with water (3×100 mL). The combined washings were extracted with chloroform (3×50 mL). The combined organic solutions were washed with brine (3×50 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 59.1 g of tert-butyl 2-(benzyloxy)ethylcarbamate as a colorless oil. the aqueous solution was extracted with chloroform (5×) The combined organic solutions were washed with water (2×) and brine (3×) dried over magnesium sulfate filtered concentrated under reduced pressure Upon concentration a white precipitate formed the organic solution was washed again with water (3×100 mL) The combined washings were extracted with chloroform (3×50 mL) The combined organic solutions were washed with brine (3×50 mL) dried over magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: Benzyltrimethylammonium chloride (4.61 g, 24.8 mmol) was added to a mixture of tert-butyl 2-hydroxyethylcarbamate (40.0 g, 248 mmol), dichloromethane (600 mL), and 50% aqueous sodium hydroxide (400 mL). Benzyl bromide (29.5 mL, 248 mmol) was then added, and the reaction was stirred for three hours. Ice water was added (1 L), and the aqueous solution was extracted with chloroform (5×). The combined organic solutions were washed with water (2×) and brine (3×), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Upon concentration, a white precipitate formed, and the organic solution was washed again with water (3×100 mL). The combined washings were extracted with chloroform (3×50 mL). The combined organic solutions were washed with brine (3×50 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure to provide 59.1 g of tert-butyl 2-(benzyloxy)ethylcarbamate as a colorless oil. the aqueous solution was extracted with chloroform (5×) The combined organic solutions were washed with water (2×) and brine (3×) dried over magnesium sulfate filtered concentrated under reduced pressure Upon concentration a white precipitate formed the organic solution was washed again with water (3×100 mL) The combined washings were extracted with chloroform (3×50 mL) The combined organic solutions were washed with brine (3×50 mL) dried over magnesium sulfate filtered concentrated under reduced pressure

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

Procedure: To a mechanically stirred mixture of tert-butyl 2-(hydroxy)ethylcarbamate (32.2 g, 200.4 mmol) and sodium hydroxide (300 mL of 50%) was added benzyltrimethylammonium chloride (3.79 g, 20.4 mmol) and benzyl bromide (23.8 mL, 200.4 mmol). After stirring at room temperature for 12 hours TLC monitoring, using 1/1 hexane/ethyl acetate and ninhydrin stain, indicated complete reaction. The resulting clear solution was diluted with ice water (1 L), and the organic layer was separated. The aqueous layer was washed with chloroform (4×). The organic layers were combined and washed with water (2×) and brine (2×), dried with sodium sulfate, and concentrated under reduced pressure to provide 45.4 g of clear liquid. NMR analysis confirmed the product, which was used in the next step. reaction the organic layer was separated The aqueous layer was washed with chloroform (4×) washed with water (2×) and brine (2×) dried with sodium sulfate concentrated under reduced pressure

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

Procedure: To a mechanically stirred mixture of tert-butyl 2-(hydroxy)ethylcarbamate (32.2 g, 200.4 mmol) and sodium hydroxide (300 mL of 50%) was added benzyltrimethylammonium chloride (3.79 g, 20.4 mmol) and benzyl bromide (23.8 mL, 200.4 mmol). After stirring at room temperature for 12 hours TLC monitoring, using 1/1 hexane/ethyl acetate and ninhydrin stain, indicated complete reaction. The resulting clear solution was diluted with ice water (1 L), and the organic layer was separated. The aqueous layer was washed with chloroform (4×). The organic layers were combined and washed with water (2×) and brine (2×), dried with sodium sulfate, and concentrated under reduced pressure to provide 45.4 g of clear liquid. NMR analysis confirmed the product, which was used in the next step. reaction the organic layer was separated The aqueous layer was washed with chloroform (4×) washed with water (2×) and brine (2×) dried with sodium sulfate concentrated under reduced pressure

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

Procedure: Dissolve (2-benzyloxyethyl)-carbamic acid tert-butyl ester (15 g) in DCM (50 mL), add trifluoroacetic acid (20 mL) and stir at 0° C. for 3 h. Concentrate and dissolve the residue in a minimal amount of DCM. Purify by chromatography on silica gel eluting sequentially with hexane/EtOAc (4:1 and 1:1), EtOAc and 2M ammonia in methanol to give the title compound (8.3 g, 85%). Concentrate dissolve the residue in a minimal amount of DCM Purify by chromatography on silica gel eluting sequentially with hexane/EtOAc (4:1 and 1:1), EtOAc and 2M ammonia in methanol

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

Procedure: Dissolve tert-butyl-N-(2-hydroxyethyl)-carbamate (10 mL, 64.5 mmol) in anhydrous THY (500 mL) at 0° C. Add sodium hydride (60% in mineral oil, 3.1 g, 77.4 mmol) and stir for 30 min at 0° C. Add benzyl bromide (9.2 mL, 77 mmol) followed by tetrabutylammonium iodide (3.7 g, 10 mmol) and stir at ambient temperature overnight. Quench with water (500 mL), extract with diethyl ether (3×100 mL), wash the combined organic extracts with brine, dry over MgSO4, filter, and evaporate to give the desired intermediate (5 g), that was used without further purification. Quench with water (500 mL) extract with diethyl ether (3×100 mL) wash the combined organic extracts with brine dry over MgSO4 filter evaporate

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

Procedure: Dissolve tert-butyl-N-(2-hydroxyethyl)-carbamate (10 mL, 64.5 mmol) in anhydrous THY (500 mL) at 0° C. Add sodium hydride (60% in mineral oil, 3.1 g, 77.4 mmol) and stir for 30 min at 0° C. Add benzyl bromide (9.2 mL, 77 mmol) followed by tetrabutylammonium iodide (3.7 g, 10 mmol) and stir at ambient temperature overnight. Quench with water (500 mL), extract with diethyl ether (3×100 mL), wash the combined organic extracts with brine, dry over MgSO4, filter, and evaporate to give the desired intermediate (5 g), that was used without further purification. Quench with water (500 mL) extract with diethyl ether (3×100 mL) wash the combined organic extracts with brine dry over MgSO4 filter evaporate

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

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

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

Procedure: Dissolve (2-benzyloxyethyl)-carbamic acid tert-butyl ester (15 g) in DCM (50 mL), add trifluoroacetic acid (20 mL) and stir at 0° C. for 3 h. Concentrate and dissolve the residue in a minimal amount of DCM. Purify by chromatography on silica gel eluting sequentially with hexane/EtOAc (4:1 and 1:1), EtOAc and 2M ammonia in methanol to give the title compound (8.3 g, 85%). Concentrate dissolve the residue in a minimal amount of DCM Purify by chromatography on silica gel eluting sequentially with hexane/EtOAc (4:1 and 1:1), EtOAc and 2M ammonia in methanol