tert-butyl N-benzyl-N-(2-oxoethyl)carbamate

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

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

Procedure: A stirred solution of (3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide (Example 8, step 4) (198 mg, 0.5 mmol) and N-benzyl-N—BOC-glycinaldehyde (0.187 g, 0.75 mmol) in anhydrous 1,2-dichloroethane (5 mL) was stirred at room temperature for 30 min, then cooled by ice bath and treated with sodium triacetoxyborohydride (212 mg, 1.0 mmol) and stirred for 3 h at room temperature. Aqueous sodium carbonate (10%, 5 mL) was added and the mixture stirred for a few minutes and extracted with ethyl acetate (30 mL, then 2×10 mL). The combined organic solution was washed with water and brine (20 mL each), dried (MgSO4), and concentrated in vacuo. The crude material was deprotected and isolated using the method described for example 8, step 5 to afford (3R,4S)-3-amino-1-(2-(benzylamino)ethyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (112 mg, 49%) as a white solid. NMR (D2O) δ 7.30-7.45 (m, 5 H), 4.21 (s, 2 H), 3.94 (d, 1H, J=12 Hz, 1 H), 3.84 (t, J=9.5 Hz, 1H), 3.60-3.75 (m, 3 H), 3.30-3.50 (m, 3 H), 2.50-2.65 (m, 1 H), 1.50-1.65 (m, 1 H), 1.10-1.35 (m, 3 H), 0.63-0.73 (m, 2 H). MS (m+1): 350.4; MS (m−H2O+1): 332.1. cooled by ice bath the mixture stirred for a few minutes extracted with ethyl acetate (30 mL The combined organic solution was washed with water and brine (20 mL each) dried (MgSO4) concentrated in vacuo isolated

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

Procedure: A stirred solution of (3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide (Example 8, step 4) (198 mg, 0.5 mmol) and N-benzyl-N-BOC-glycinaldehyde (0.187 g, 0.75 mmol) in anhydrous 1,2-dichloroethane (5 mL) was stirred at room temperature for 30 min, then cooled by ice bath and treated with sodium triacetoxyborohydride (212 mg, 1.0 mmol) and stirred for 3 h at room temperature. Aqueous sodium carbonate (10%, 5 mL) was added and the mixture stirred for a few minutes and extracted with ethyl acetate (30 mL, then 2×10 mL). The combined organic solution was washed with water and brine (20 mL each), dried (MgSO4), and concentrated in vacuo. The crude material was deprotected and isolated using the method described for example 8, step 5 to afford (3R,4S)-3-amino-1-(2-(benzylamino)ethyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (112 mg, 49%) as a white solid. NMR (D2O) δ 7.30-7.45 (m, 5 H), 4.21 (s, 2 H), 3.94 (d, 1 H, J=12 Hz, 1 H), 3.84 (t, J=9.5 Hz, 1 H), 3.60-3.75 (m, 3 H), 3.30-3.50 (m, 3 H), 2.50-2.65 (m, 1 H), 1.50-1.65 (m, 1 H), 1.10-1.35 m, 3 H), 0.63-0.73 (m, 2 H). MS (m+1): 350.4; MS (m−H2O+1): 332.1. cooled by ice bath the mixture stirred for a few minutes extracted with ethyl acetate (30 mL The combined organic solution was washed with water and brine (20 mL each) dried (MgSO4) concentrated in vacuo isolated

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

Procedure: A stirred solution of (3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide (Example 8, step 4) (198 mg, 0.5 mmol) and N-benzyl-N-BOC-glycinaldehyde (0.187 g, 0.75 mmol) in anhydrous 1,2-dichloroethane (5 mL) was stirred at room temperature for 30 min, then cooled by ice bath and treated with sodium triacetoxyborohydride (212 mg, 1.0 mmol) and stirred for 3 h at room temperature. Aqueous sodium carbonate (10%, 5 mL) was added and the mixture stirred for a few minutes and extracted with ethyl acetate (30 mL, then 2×10 mL). The combined organic solution was washed with water and brine (20 mL each), dried (MgSO4), and concentrated in vacuo. The crude material was deprotected and isolated using the method described for example 8, step 5 to afford (3R,4S)-3-amino-1-(2-(benzylamino)ethyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (112 mg, 49%) as a white solid. NMR (D2O) δ 7.30-7.45 (m, 5 H), 4.21 (s, 2 H), 3.94 (d, 1 H, J=12 Hz, 1 H), 3.84 (t, J=9.5 Hz, 1 H), 3.60-3.75 (m, 3 H), 3.30-3.50 (m, 3 H), 2.50-2.65 (m, 1 H), 1.50-1.65 (m, 1 H), 1.10-1.35 m, 3 H), 0.63-0.73 (m, 2 H). MS (m+1): 350.4; MS (m−H2O+1): 332.1. cooled by ice bath the mixture stirred for a few minutes extracted with ethyl acetate (30 mL The combined organic solution was washed with water and brine (20 mL each) dried (MgSO4) concentrated in vacuo isolated

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

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

Procedure: 8 mg of 3-benzyl-6-fluoro-1,2,3,4-tetrahydroisoquinoline, 9.3 mg of tert-butyl benzyl(2-oxoethyl)carbamate, 11 mg of sodium triacetoxyborohydride, and 10 μL of acetic acid were dissolved in 0.5 mL of toluene, followed by continuously stirring at room temperature for 30 minutes. Water was added to the reaction liquid, followed by extraction with ethyl acetate, and the organic layer was then washed with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue obtained was purified using silica gel chromatography (diethyl ether:hexane=1:2) to obtain 14 mg (yield 85%) of a title compound as a yellow oily substance. followed by extraction with ethyl acetate the organic layer was then washed with an aqueous sodium bicarbonate solution and saturated brine dried over anhydrous sodium sulfate concentrated under reduced pressure The residue obtained was purified

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

Procedure: 8 mg of 3-benzyl-6-fluoro-1,2,3,4-tetrahydroisoquinoline, 9.3 mg of tert-butyl benzyl(2-oxoethyl)carbamate, 11 mg of sodium triacetoxyborohydride, and 10 μL of acetic acid were dissolved in 0.5 mL of toluene, followed by continuously stirring at room temperature for 30 minutes. Water was added to the reaction liquid, followed by extraction with ethyl acetate, and the organic layer was then washed with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue obtained was purified using silica gel chromatography (diethyl ether:hexane=1:2) to obtain 14 mg (yield 85%) of a title compound as a yellow oily substance. followed by extraction with ethyl acetate the organic layer was then washed with an aqueous sodium bicarbonate solution and saturated brine dried over anhydrous sodium sulfate concentrated under reduced pressure The residue obtained was purified

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

Procedure: 8 mg of 3-benzyl-6-fluoro-1,2,3,4-tetrahydroisoquinoline, 9.3 mg of tert-butyl benzyl(2-oxoethyl)carbamate, 11 mg of sodium triacetoxyborohydride, and 10 μL of acetic acid were dissolved in 0.5 mL of toluene, followed by continuously stirring at room temperature for 30 minutes. Water was added to the reaction liquid, followed by extraction with ethyl acetate, and the organic layer was then washed with an aqueous sodium bicarbonate solution and saturated brine, dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue obtained was purified using silica gel chromatography (diethyl ether:hexane=1:2) to obtain 14 mg (yield 85%) of a title compound as a yellow oily substance. followed by extraction with ethyl acetate the organic layer was then washed with an aqueous sodium bicarbonate solution and saturated brine dried over anhydrous sodium sulfate concentrated under reduced pressure The residue obtained was purified

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

Procedure: A stirred solution of (3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide (Example 8, step 4) (198 mg, 0.5 mmol) and N-benzyl-N—BOC-glycinaldehyde (0.187 g, 0.75 mmol) in anhydrous 1,2-dichloroethane (5 mL) was stirred at room temperature for 30 min, then cooled by ice bath and treated with sodium triacetoxyborohydride (212 mg, 1.0 mmol) and stirred for 3 h at room temperature. Aqueous sodium carbonate (10%, 5 mL) was added and the mixture stirred for a few minutes and extracted with ethyl acetate (30 mL, then 2×10 mL). The combined organic solution was washed with water and brine (20 mL each), dried (MgSO4), and concentrated in vacuo. The crude material was deprotected and isolated using the method described for example 8, step 5 to afford (3R,4S)-3-amino-1-(2-(benzylamino)ethyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (112 mg, 49%) as a white solid. NMR (D2O) δ 7.30-7.45 (m, 5 H), 4.21 (s, 2 H), 3.94 (d, 1H, J=12 Hz, 1 H), 3.84 (t, J=9.5 Hz, 1H), 3.60-3.75 (m, 3 H), 3.30-3.50 (m, 3 H), 2.50-2.65 (m, 1 H), 1.50-1.65 (m, 1 H), 1.10-1.35 (m, 3 H), 0.63-0.73 (m, 2 H). MS (m+1): 350.4; MS (m−H2O+1): 332.1. cooled by ice bath the mixture stirred for a few minutes extracted with ethyl acetate (30 mL The combined organic solution was washed with water and brine (20 mL each) dried (MgSO4) concentrated in vacuo isolated

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

Procedure: A stirred solution of (3R,4S)-3-acetamido-N-tert-butyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-3-carboxamide (Example 8, step 4) (198 mg, 0.5 mmol) and N-benzyl-N-BOC-glycinaldehyde (0.187 g, 0.75 mmol) in anhydrous 1,2-dichloroethane (5 mL) was stirred at room temperature for 30 min, then cooled by ice bath and treated with sodium triacetoxyborohydride (212 mg, 1.0 mmol) and stirred for 3 h at room temperature. Aqueous sodium carbonate (10%, 5 mL) was added and the mixture stirred for a few minutes and extracted with ethyl acetate (30 mL, then 2×10 mL). The combined organic solution was washed with water and brine (20 mL each), dried (MgSO4), and concentrated in vacuo. The crude material was deprotected and isolated using the method described for example 8, step 5 to afford (3R,4S)-3-amino-1-(2-(benzylamino)ethyl)-4-(3-boronopropyl)pyrrolidine-3-carboxylic acid (112 mg, 49%) as a white solid. NMR (D2O) δ 7.30-7.45 (m, 5 H), 4.21 (s, 2 H), 3.94 (d, 1 H, J=12 Hz, 1 H), 3.84 (t, J=9.5 Hz, 1 H), 3.60-3.75 (m, 3 H), 3.30-3.50 (m, 3 H), 2.50-2.65 (m, 1 H), 1.50-1.65 (m, 1 H), 1.10-1.35 m, 3 H), 0.63-0.73 (m, 2 H). MS (m+1): 350.4; MS (m−H2O+1): 332.1. cooled by ice bath the mixture stirred for a few minutes extracted with ethyl acetate (30 mL The combined organic solution was washed with water and brine (20 mL each) dried (MgSO4) concentrated in vacuo isolated