tert-butyl 3-(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxobutanoate

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

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

Procedure: To a suspension of 3-(9H-Fluoren-9-ylmethoxycarbonylamino)-4-oxo-butyric acid tert-butyl ester (1.24 g, 3.14 mmol) in Dichloromethane (10 mL) at room temperature was added 0.20 equiv TsOH.H2O (0.12 g, 0.63 mmol) and followed by dropwise 5.0 equiv of Benzyl alcohol (1.62 mL, 15.68 mmol). After stirring room temperature for 18 hrs, the reaction mixture was filtered through celite and the filtrate was concentrated in vacuo to obtain a crude title compound. The residue was purified by flask column chromatography on silica gel eluting with EtOAc/Hexane (10–40%) to give the title compound (0.75 g, 40%) as clear oil. TLC (40% EtOAc/Hexane) Rf=0.68; 1HNMR (CDCl3) δ 7.76 (d, J=7.2 Hz, 2H), 7.59 (d, J=7.5 Hz, 2H), 7.39 (t, J=7.5 Hz, 21H), 7.35–7.27 (m, 12H), 5.37 (d, J=9.6 Hz, 1H), 4.73–4.52 (m, 5H), 4.35 (d, J=6.6 Hz, 2H), 4.24–4.16 (q, J=6.6 Hz, 2H), 2.55–2.50 (m, 2H), 1.39 (s, 9H). MS(ES) for C37H39NO9 (MW=593.71): positive 611 (M+NH4+). the reaction mixture was filtered through celite the filtrate was concentrated in vacuo to obtain a crude title compound The residue was purified by flask column chromatography on silica gel eluting with EtOAc/Hexane (10–40%)

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

Procedure: To a suspension of 3-(9H-Fluoren-9-ylmethoxycarbonylamino)-N-methoxy-N-methyl-succinamic acid tert-butyl ester (4.57 g, 10.04 mmol) in Ethyl ether (30 mL) at −5° C. was added dropwise 0.5 equiv of 1.0M Lithium aluminum hydride (LAH) in ethyl ether (5.02 mL, 5.02 mmol). After stirring at −5° C. to room temperature for 1 hr, the reaction mixture was treated with 5% KHSO4 (200 mL), stirred for 5 min and then partitioned between EtOAc/water. The organic phase was washed with saturated NaCl solution (200 mL), dried over Na2SO4 and evaporated to dryness. The residue was purified by flask column chromatography on silica gel eluting with EtOAc/Hexane (20%) to give the title compound (2.18 g, 55%) as a clear oil. TLC (30% EtOAc/Hexane) Rf=0.35; 1HNMR (CDCl3) δ 9.65 (s, 1H), 7.77 (d, J=7.2 Hz, 2H), 7.50 (d, J=7.5 Hz, 2H), 7.41 (t, J=7.5 Hz, 2H), 7.33 (dt, J=7.5, 1.2 Hz, 2H), 5.88 (d, J=7.2 Hz, 1H), 4.50–4.36 (m, 2H), 4.24 (t, J=6.6 Hz, 1H), 3.54–3.45 (m, 1H), 3.00–2.93 (dd, J=17.4, 4.8 Hz, 1H), 2.82–274 (dd, J=17.7, 5.1s Hz, 1H), 1.45 (s, 9H). MS(ES) for C23H25NO5 (MW=395.45): positive 396 (MH+). stirred for 5 min partitioned between EtOAc/water The organic phase was washed with saturated NaCl solution (200 mL) dried over Na2SO4 evaporated to dryness The residue was purified by flask column chromatography on silica gel eluting with EtOAc/Hexane (20%)

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

Procedure: To a suspension of 3-(9H-Fluoren-9-ylmethoxycarbonylamino)-4-oxo-butyric acid tert-butyl ester (1.24 g, 3.14 mmol) in Dichloromethane (10 mL) at room temperature was added 0.20 equiv TsOH.H2O (0.12 g, 0.63 mmol) and followed by dropwise 5.0 equiv of Benzyl alcohol (1.62 mL, 15.68 mmol). After stirring room temperature for 18 hrs, the reaction mixture was filtered through celite and the filtrate was concentrated in vacuo to obtain a crude title compound. The residue was purified by flask column chromatography on silica gel eluting with EtOAc/Hexane (10–40%) to give the title compound (0.75 g, 40%) as clear oil. TLC (40% EtOAc/Hexane) Rf=0.68; 1HNMR (CDCl3) δ 7.76 (d, J=7.2 Hz, 2H), 7.59 (d, J=7.5 Hz, 2H), 7.39 (t, J=7.5 Hz, 21H), 7.35–7.27 (m, 12H), 5.37 (d, J=9.6 Hz, 1H), 4.73–4.52 (m, 5H), 4.35 (d, J=6.6 Hz, 2H), 4.24–4.16 (q, J=6.6 Hz, 2H), 2.55–2.50 (m, 2H), 1.39 (s, 9H). MS(ES) for C37H39NO9 (MW=593.71): positive 611 (M+NH4+). the reaction mixture was filtered through celite the filtrate was concentrated in vacuo to obtain a crude title compound The residue was purified by flask column chromatography on silica gel eluting with EtOAc/Hexane (10–40%)

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

Procedure: To a suspension of 3-(9H-Fluoren-9-ylmethoxycarbonylamino)-N-methoxy-N-methyl-succinamic acid tert-butyl ester (4.57 g, 10.04 mmol) in Ethyl ether (30 mL) at −5° C. was added dropwise 0.5 equiv of 1.0M Lithium aluminum hydride (LAH) in ethyl ether (5.02 mL, 5.02 mmol). After stirring at −5° C. to room temperature for 1 hr, the reaction mixture was treated with 5% KHSO4 (200 mL), stirred for 5 min and then partitioned between EtOAc/water. The organic phase was washed with saturated NaCl solution (200 mL), dried over Na2SO4 and evaporated to dryness. The residue was purified by flask column chromatography on silica gel eluting with EtOAc/Hexane (20%) to give the title compound (2.18 g, 55%) as a clear oil. TLC (30% EtOAc/Hexane) Rf=0.35; 1HNMR (CDCl3) δ 9.65 (s, 1H), 7.77 (d, J=7.2 Hz, 2H), 7.50 (d, J=7.5 Hz, 2H), 7.41 (t, J=7.5 Hz, 2H), 7.33 (dt, J=7.5, 1.2 Hz, 2H), 5.88 (d, J=7.2 Hz, 1H), 4.50–4.36 (m, 2H), 4.24 (t, J=6.6 Hz, 1H), 3.54–3.45 (m, 1H), 3.00–2.93 (dd, J=17.4, 4.8 Hz, 1H), 2.82–274 (dd, J=17.7, 5.1s Hz, 1H), 1.45 (s, 9H). MS(ES) for C23H25NO5 (MW=395.45): positive 396 (MH+). stirred for 5 min partitioned between EtOAc/water The organic phase was washed with saturated NaCl solution (200 mL) dried over Na2SO4 evaporated to dryness The residue was purified by flask column chromatography on silica gel eluting with EtOAc/Hexane (20%)

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

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

Procedure: To a suspension of 3-(9H-Fluoren-9-ylmethoxycarbonylamino)-4-oxo-butyric acid tert-butyl ester (1.24 g, 3.14 mmol) in Dichloromethane (10 mL) at room temperature was added 0.20 equiv TsOH.H2O (0.12 g, 0.63 mmol) and followed by dropwise 5.0 equiv of Benzyl alcohol (1.62 mL, 15.68 mmol). After stirring room temperature for 18 hrs, the reaction mixture was filtered through celite and the filtrate was concentrated in vacuo to obtain a crude title compound. The residue was purified by flask column chromatography on silica gel eluting with EtOAc/Hexane (10–40%) to give the title compound (0.75 g, 40%) as clear oil. TLC (40% EtOAc/Hexane) Rf=0.68; 1HNMR (CDCl3) δ 7.76 (d, J=7.2 Hz, 2H), 7.59 (d, J=7.5 Hz, 2H), 7.39 (t, J=7.5 Hz, 21H), 7.35–7.27 (m, 12H), 5.37 (d, J=9.6 Hz, 1H), 4.73–4.52 (m, 5H), 4.35 (d, J=6.6 Hz, 2H), 4.24–4.16 (q, J=6.6 Hz, 2H), 2.55–2.50 (m, 2H), 1.39 (s, 9H). MS(ES) for C37H39NO9 (MW=593.71): positive 611 (M+NH4+). the reaction mixture was filtered through celite the filtrate was concentrated in vacuo to obtain a crude title compound The residue was purified by flask column chromatography on silica gel eluting with EtOAc/Hexane (10–40%)

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

Procedure: To a suspension of 3-(9H-Fluoren-9-ylmethoxycarbonylamino)-N-methoxy-N-methyl-succinamic acid tert-butyl ester (4.57 g, 10.04 mmol) in Ethyl ether (30 mL) at −5° C. was added dropwise 0.5 equiv of 1.0M Lithium aluminum hydride (LAH) in ethyl ether (5.02 mL, 5.02 mmol). After stirring at −5° C. to room temperature for 1 hr, the reaction mixture was treated with 5% KHSO4 (200 mL), stirred for 5 min and then partitioned between EtOAc/water. The organic phase was washed with saturated NaCl solution (200 mL), dried over Na2SO4 and evaporated to dryness. The residue was purified by flask column chromatography on silica gel eluting with EtOAc/Hexane (20%) to give the title compound (2.18 g, 55%) as a clear oil. TLC (30% EtOAc/Hexane) Rf=0.35; 1HNMR (CDCl3) δ 9.65 (s, 1H), 7.77 (d, J=7.2 Hz, 2H), 7.50 (d, J=7.5 Hz, 2H), 7.41 (t, J=7.5 Hz, 2H), 7.33 (dt, J=7.5, 1.2 Hz, 2H), 5.88 (d, J=7.2 Hz, 1H), 4.50–4.36 (m, 2H), 4.24 (t, J=6.6 Hz, 1H), 3.54–3.45 (m, 1H), 3.00–2.93 (dd, J=17.4, 4.8 Hz, 1H), 2.82–274 (dd, J=17.7, 5.1s Hz, 1H), 1.45 (s, 9H). MS(ES) for C23H25NO5 (MW=395.45): positive 396 (MH+). stirred for 5 min partitioned between EtOAc/water The organic phase was washed with saturated NaCl solution (200 mL) dried over Na2SO4 evaporated to dryness The residue was purified by flask column chromatography on silica gel eluting with EtOAc/Hexane (20%)