tert-butyl N-[2-(methylamino)ethyl]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:

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

Procedure: To a solution of (2-amino-ethyl)-carbamic acid-tert-butyl ester (5 g) and triethylamine (6.5 ml) in tetrahydrofuran (1000 ml) at 0° C. was added methyliodide (1.94 ml) dropwise over a period of 1 hour. The mixture was allowed to warm to ambient temperature and stirred for 72 hours before removal of solvents by evaporation. The residue was partitioned between ethyl acetate and water. The organic layer was separated, dried (MgSO4) and solvent removed by evaporation to give the title compound (3.7 g). The residue was partitioned between ethyl acetate and water The organic layer was separated dried (MgSO4) and solvent removed by evaporation

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

Procedure: A mixture of 3-iodo-1-(oxan-2-yl)-1H-pyrazole-4-carbaldehyde (3.2 g, 10.45 mmol, 1.00 equiv), tert-butyl N-[2-(methylamino)ethyl]carbamate (2.2 g, 12.63 mmol, 1.21 equiv) and NaBH(OAc)3 (6.65 g, 31.38 mmol, 3.00 equiv) in dichloroethane (30 mL) was stirred for 2 h at room temperature. The reaction was quenched with 50 mL of saturated aqueous sodium bicarbonate solution. The resulting mixture was extracted with 3×200 mL of dichloromethane. The combined organic layers was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified on a silica gel column eluted with 30-100% ethyl acetate in petroleum ether to give 4.05 g (83%) of tert-butyl (2-(((3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)methyl)(methyl)amino)ethyl)carbamate as a light yellow oil. H NMR (300 MHz, CDCl3): δ 7.48 (s, 1H), 5.35-5.30 (m, 1H), 4.13-4.03 (m, 1H), 3.71-3.63 (m, 1H), 3.36 (s, 2H), 3.26-3.25 (m, 2H), 2.52-2.49 (m, 2H), 2.21 (s, 3H), 2.09-2.01 (m, 3H), 1.68-1.58 (m, 3H), 1.44 (s, 9H) ppm. LCMS (method C, ESI): RT=0.58 min, m/z=465.0 [M+H]. The reaction was quenched with 50 mL of saturated aqueous sodium bicarbonate solution The resulting mixture was extracted with 3×200 mL of dichloromethane The combined organic layers was dried over anhydrous sodium sulfate concentrated under vacuum The residue was purified on a silica gel column eluted with 30-100% ethyl acetate in petroleum ether

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

Procedure: To a mixture of tert-butyl 2-(methylamino)ethylcarbamate (0.348 g, 2 mmol), 2-hydroxybenzoyl chloride (0.276 g, 2 mmol) and imidazole (0.136 g, 2 mmol) in ethyl acetate (8 mL) at 0° C. was slowly added a solution of DCC (0.412 g, 2 mmol) in ethyl acetate (2 mL). The mixture was stirred (RT, 16 h), filtered and concentrated under reduced pressure. The crude material was purified by chromatography on silica gel, eluting with ethyl acetate/petroleum ether (20-50%) to afford tert-butyl 2-(2-hydroxy-N-methylbenzamido)ethylcarbamate (0.2 g, 34%) as a colorless oil. 1HNMR (CDCl3): δ7.5 (m, 2H, CH), 7.0 (d, 1H, CH), 6.8 (d, 1H, CH), 3.7 (m, 2H, CH2), 3.48 (m, 2H, CH2), 3.2 (m, 3H, CH3), 1.5 (s, 9H, CH3). filtered concentrated under reduced pressure The crude material was purified by chromatography on silica gel eluting with ethyl acetate/petroleum ether (20-50%)

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

Procedure: A mixture of tert-butyl 2-(benzyl(methyl)amino)ethylcarbamate (1.20 g, 4.54 mmol), 10% Pd/C (0.90 g) and MeOH (60 ml) was stirred under a H2 atmosphere (0.8 MPa, RT, 16 h). The mixture was filtered and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel, eluting with saturated NH3 in MeOH-DCM (0-10%) to afford tert-butyl 2-(methylamino)ethylcarbamate as a colorless oil (0.54 g, 68.3%). 1HNMR (CDCl3): δ3.25 (m, 2H, CH2), 2.7 (m, 2H, CH2), 2.49 (s, 3H, CH3), 1.49 (s, 9H, CH3). The mixture was filtered concentrated under reduced pressure The crude material was purified by column chromatography on silica gel eluting with saturated NH3 in MeOH-DCM (0-10%)

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

Procedure: A mixture of tert-butyl 2-(benzyl(methyl)amino)ethylcarbamate (1.20 g, 4.54 mmol), 10% Pd/C (0.90 g) and MeOH (60 ml) was stirred under a H2 atmosphere (0.8 MPa, RT, 16 h). The mixture was filtered and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel, eluting with saturated NH3 in MeOH-DCM (0-10%) to afford tert-butyl 2-(methylamino)ethylcarbamate as a colorless oil (0.54 g, 68.3%). 1HNMR (CDCl3): δ3.25 (m, 2H, CH2), 2.7 (m, 2H, CH2), 2.49 (s, 3H, CH3), 1.49 (s, 9H, CH3). The mixture was filtered concentrated under reduced pressure The crude material was purified by column chromatography on silica gel eluting with saturated NH3 in MeOH-DCM (0-10%)

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

Procedure: To a mixture of tert-butyl 2-(methylamino)ethylcarbamate (0.348 g, 2 mmol), 2-hydroxybenzoyl chloride (0.276 g, 2 mmol) and imidazole (0.136 g, 2 mmol) in ethyl acetate (8 mL) at 0° C. was slowly added a solution of DCC (0.412 g, 2 mmol) in ethyl acetate (2 mL). The mixture was stirred (RT, 16 h), filtered and concentrated under reduced pressure. The crude material was purified by chromatography on silica gel, eluting with ethyl acetate/petroleum ether (20-50%) to afford tert-butyl 2-(2-hydroxy-N-methylbenzamido)ethylcarbamate (0.2 g, 34%) as a colorless oil. 1HNMR (CDCl3): δ7.5 (m, 2H, CH), 7.0 (d, 1H, CH), 6.8 (d, 1H, CH), 3.7 (m, 2H, CH2), 3.48 (m, 2H, CH2), 3.2 (m, 3H, CH3), 1.5 (s, 9H, CH3). filtered concentrated under reduced pressure The crude material was purified by chromatography on silica gel eluting with ethyl acetate/petroleum ether (20-50%)

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

Procedure: A mixture of tert-butyl 2-(benzyl(methyl)amino)ethylcarbamate (1.20 g, 4.54 mmol), 10% Pd/C (0.90 g) and MeOH (60 ml) was stirred under a H2 atmosphere (0.8 MPa, RT, 16 h). The mixture was filtered and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel, eluting with saturated NH3 in MeOH-DCM (0-10%) to afford tert-butyl 2-(methylamino)ethylcarbamate as a colorless oil (0.54 g, 68.3%). 1HNMR (CDCl3): δ3.25 (m, 2H, CH2), 2.7 (m, 2H, CH2), 2.49 (s, 3H, CH3), 1.49 (s, 9H, CH3). The mixture was filtered concentrated under reduced pressure The crude material was purified by column chromatography on silica gel eluting with saturated NH3 in MeOH-DCM (0-10%)

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

Procedure: A mixture of tert-butyl 2-(benzyl(methyl)amino)ethylcarbamate (1.20 g, 4.54 mmol), 10% Pd/C (0.90 g) and MeOH (60 ml) was stirred under a H2 atmosphere (0.8 MPa, RT, 16 h). The mixture was filtered and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel, eluting with saturated NH3 in MeOH-DCM (0-10%) to afford tert-butyl 2-(methylamino)ethylcarbamate as a colorless oil (0.54 g, 68.3%). 1HNMR (CDCl3): δ3.25 (m, 2H, CH2), 2.7 (m, 2H, CH2), 2.49 (s, 3H, CH3), 1.49 (s, 9H, CH3). The mixture was filtered concentrated under reduced pressure The crude material was purified by column chromatography on silica gel eluting with saturated NH3 in MeOH-DCM (0-10%)