tert-butyl N-[[4-(hydroxymethyl)phenyl]methyl]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:; See reaction.notes.procedure_details.

Procedure: The compound (18.0 g) obtained in Example 103-2 was dissolved in chloroform (540 ml) and then added with manganese dioxide (chemically processed product) (118 g), followed by stirring at room temperature for 15 hours. The reaction solution was filtrated through Celite and the filtrate was then concentrated under reduced pressure. The residue was purified through silica gel column chromatography (chloroform/ethyl acetate), thereby obtaining the subject compound (17.1 g) as a white solid. The reaction solution was filtrated through Celite the filtrate was then concentrated under reduced pressure The residue was purified through silica gel column chromatography (chloroform/ethyl acetate)

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

Procedure: Lithium aluminum hydride (5.21 g) was suspended in THF (243 ml). Then, a solution of the compound (24.3 g) obtained in Example 103-1 in THF (243 ml) was gradually added to the suspension over 50 minutes while stirring under ice-cooling, followed by stirring at room temperature for 1 hour. The reaction solution was added with sodium sulfate decahydrate and a 20% sodium hydroxide aqueous solution and then filtrated through Celite. The filtrate was concentrated under reduced pressure and dried under vacuum, thereby obtaining the subject compound (18.5 g). cooling by stirring at room temperature for 1 hour a 20% sodium hydroxide aqueous solution and then filtrated through Celite The filtrate was concentrated under reduced pressure dried under vacuum

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: A suspension of 1.40 g (36.8 mmol) of lithium aluminum hydride in 150 ml of tetrahydrofuran was stirred at 0° C. A solution of 13.0 g (49.0 mmol) of 4-(tert-butoxycarbonylaminomethyl)benzoate in 50 ml of tetrahydrofuran was dropwise added slowly to the suspension. After completion of the dropwise addition, the solution was heated to reflux for 2 hours and then cooled to 0° C. After 20 ml of 50% tetrahydrofuran was dropwise added to the reaction mixture, 100 ml of ethyl acetate was added thereto. Insoluble matters were filtered off and the resulting filtrate was concentrated under reduced pressure. The concentrate was isolated and purified by silica gel column chromatography to obtain 8.80 g (75.7%) of 4-(tert-butoxycarbonylaminomethyl)benzyl alcohol. After completion of the dropwise addition the solution was heated to reflux for 2 hours cooled to 0° C was added Insoluble matters were filtered off the resulting filtrate was concentrated under reduced pressure The concentrate was isolated purified by silica gel column chromatography

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

Procedure: A suspension of 1.40 g (36.8 mmol) of lithium aluminum hydride in 150 ml of tetrahydrofuran was stirred at 0° C. A solution of 13.0 g (49.0 imol) of 4-(tert-butoxycarbonylaminomethyl)benzoate in 50 ml of tetrahydrofuran was dropwise added slowly to the suspension. After completion of the dropwise addition, the solution was heated to reflux for 2 hours and then cooled to 0° C. After 20 ml of 50% tetrahydrofuran was dropwise added to the reaction mixture, 100 ml of ethyl acetate was added thereto. Insoluble matters were filtered off and the resulting filtrate was concentrated under reduced pressure. The concentrate was isolated and purified by silica gel column chromatography to obtain 8.80 g (75.7%) of 4-(tert-butoxycarbonylaminomethyl)benzyl alcohol. After completion of the dropwise addition the solution was heated to reflux for 2 hours cooled to 0° C was added Insoluble matters were filtered off the resulting filtrate was concentrated under reduced pressure The concentrate was isolated purified by silica gel column chromatography

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

Procedure: (4-Hydroxymethyl-benzyl)-carbamic acid tert-butyl ester (480 mg, 0.71 mmol) was dissolved in DCM (3 mL) and cooled to −78° C. (dry ice/acetone). Dess-Martin periodinane (331 mg, 0.78 mmol) was added to the reaction which was allowed to warm to r.t and stir for 3 h. A 1:1 solution of saturated sodium bicarbonate and sodium sulfite (20 mL) was added and the reaction mixture stirred vigorously for 15 min. The organic layer was isolated, washed with saturated sodium bicarbonate (10 mL), dried (Na2SO4) and evaporated to dryness to afford the desired compound (480 mg, 100%). m/z 258 [M++Na]+ to warm the reaction mixture stirred vigorously for 15 min The organic layer was isolated washed with saturated sodium bicarbonate (10 mL) dried (Na2SO4) evaporated to dryness

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

Procedure: LiAl4 (227 mg, 5.97 mmol) was slurried in a mixture of THF (5 mL) and dioxane (5 mL) and cooled to 0° C. under an atmosphere of N2. 4-(tert-Butoxycarbonylamino-methyl)-benzoic acid was dissolved in a mixture of THF (5 mL) and dioxane (5 mL) and added to the chilled solution drop-wise over 15 min. The reaction mixture was allowed to warm to r.t and stirred for 16 h. Water (1 mL) was added to the reaction mixture which was then filtered through celite. The filtrate was evaporated to dryness and the residue partitioned between EtOAc (25 mL) and water (25 mL). The aqueous layer was extracted with EtOAC (2×25 mL), the organic layers combined, dried (Na2SO4) and evaporated to dryness to afford the desired product (460 mg, 100%). m/z 260 [M++Na]+ added to the chilled solution drop-wise over 15 min to warm was then filtered through celite The filtrate was evaporated to dryness the residue partitioned between EtOAc (25 mL) and water (25 mL) The aqueous layer was extracted with EtOAC (2×25 mL) dried (Na2SO4) evaporated to dryness

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

Procedure: LiAl4 (227 mg, 5.97 mmol) was slurried in a mixture of THF (5 mL) and dioxane (5 mL) and cooled to 0° C. under an atmosphere of N2. 4-(tert-Butoxycarbonylamino-methyl)-benzoic acid was dissolved in a mixture of THF (5 mL) and dioxane (5 mL) and added to the chilled solution drop-wise over 15 min. The reaction mixture was allowed to warm to r.t and stirred for 16 h. Water (1 mL) was added to the reaction mixture which was then filtered through celite. The filtrate was evaporated to dryness and the residue partitioned between EtOAc (25 mL) and water (25 mL). The aqueous layer was extracted with EtOAC (2×25 mL), the organic layers combined, dried (Na2SO4) and evaporated to dryness to afford the desired product (460 mg, 100%). m/z 260 [M++Na]+ added to the chilled solution drop-wise over 15 min to warm was then filtered through celite The filtrate was evaporated to dryness the residue partitioned between EtOAc (25 mL) and water (25 mL) The aqueous layer was extracted with EtOAC (2×25 mL) dried (Na2SO4) evaporated to dryness