N-[2-(tert-ButyldiMethylsilyloxy)ethyl]MethylaMine

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: 2,4-Difluorobenzenesulfonyl chloride (1 g, 4.70 mmol) in DCM (2 mL) was added slowly to a solution of (2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)methylamine (980 mg, 5.17 mmol) in DCM (65 mL) and 10% sodium hydroxide solution (65 mL) at 0° C. The reaction was allowed to warm to RT and stirred for 20 hours. The DCM layer was separated and the aqueous re-extracted into DCM (2×50 mL). The combined organics were washed with brine (80 mL), dried (MgSO4), and reduced in vacuo to give the desired compound as a colourless oil (0.7 g). 1H NMR δ (CDCl3): 0.00 (s, 6H), 0.83 (s, 9H), 2.91 (s, 3H), 3.24 (t, 2H), 3.73 (t, 2H), 6.87-6.96 (m, 2H), 7.82-7.88 (m, 1H) The DCM layer was separated the aqueous re-extracted into DCM (2×50 mL) The combined organics were washed with brine (80 mL) dried (MgSO4)

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

Procedure: 2,4-Difluorobenzenesulfonyl chloride (1 g, 4.70 mmol) in DCM (2 mL) was added slowly to a solution of (2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)methylamine (980 mg, 5.17 mmol) in DCM (65 mL) and 10% sodium hydroxide solution (65 mL) at 0° C. The reaction was allowed to warm to RT and stirred for 20 hours. The DCM layer was separated and the aqueous re-extracted into DCM (2×50 mL). The combined organics were washed with brine (80 mL), dried (MgSO4), and reduced in vacuo to give the desired compound as a colourless oil (0.7 g). 1H NMR δ (CDCl3): 0.00 (s, 6H), 0.83 (s, 9H), 2.91 (s, 3H), 3.24 (t, 2H), 3.73 (t, 2H), 6.87-6.96 (m, 2H), 7.82-7.88 (m, 1H) The DCM layer was separated the aqueous re-extracted into DCM (2×50 mL) The combined organics were washed with brine (80 mL) dried (MgSO4)

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

Procedure: 2,3,4-Trifluorobenzoyl chloride (2.32 mL, 18.16 mmol) was added slowly to a stirred mixture of (2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)methylamine (3.44 g, 18.16 mmol) in DCM (200 mL) and 10% aqueous sodium hydroxide solution (200 mL) at 0° C. The reaction was allowed to warm to RT and stirred for a further 24 hours. The phases were separated and the aqueous phase further extracted with DCM (3×100 mL), the combined organics dried (MgSO4), filtered and the solvent removed in vacuo to give a pale yellow oil. The residue was chromatographed on silica, eluting with 0-50% ethyl acetate in isohexane, to give the desired compound as a colourless oil (5.22 g). The phases were separated the aqueous phase further extracted with DCM (3×100 mL) the combined organics dried (MgSO4) filtered the solvent removed in vacuo to give a pale yellow oil The residue was chromatographed on silica eluting with 0-50% ethyl acetate in isohexane

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

Procedure: DIPEA (2.45 mL, 14.0 mmol) and tert-butyldimethylsilyl chloride (1.51 g, 10.0 mmol) were added to a solution of 2-(methylamino)ethanol (751 mg, 10.0 mmol) in dry DCM (25 mL) under argon and the reaction mixture allowed to stir at RT for 16 hours. Diethyl ether (50 mL) and water (50 mL) were added to the reaction mixture and the aqueous phase was extracted with diethyl ether (3×30 mL). The combined extracts were dried (MgSO4), filtered and evaporated to give a pale yellow oil which was dried under high vacuum to give the title compound (1.91 g). the aqueous phase was extracted with diethyl ether (3×30 mL) The combined extracts were dried (MgSO4) filtered evaporated to give a pale yellow oil which was dried under high vacuum

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

Procedure: DIPEA (2.45 mL, 14.0 mmol) and tert-butyldimethylsilyl chloride (1.51 g, 10.0 mmol) were added to a solution of 2-(methylamino)ethanol (751 mg, 10.0 mmol) in dry DCM (25 mL) under argon and the reaction mixture allowed to stir at RT for 16 hours. Diethyl ether (50 mL) and water (50 mL) were added to the reaction mixture and the aqueous phase was extracted with diethyl ether (3×30 mL). The combined extracts were dried (MgSO4), filtered and evaporated to give a pale yellow oil which was dried under high vacuum to give the title compound (1.91 g). the aqueous phase was extracted with diethyl ether (3×30 mL) The combined extracts were dried (MgSO4) filtered evaporated to give a pale yellow oil which was dried under high vacuum

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

Procedure: 3-Chloro-2,4-difluorobenzoyl chloride (1.92 g, 9.1 mmol) was added slowly to a stirred solution of (2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)methylamine (1.89 g, 10.0 mmol) in a 1:1 mixture of 10% sodium hydroxide solution and DCM at 0° C. The reaction mixture was then allowed to warm up to RT and left to stir for 5 hours. The phases were separated and the aqueous phase was extracted with DCM (3×50 mL). The combined extracts were dried (MgSO4), filtered and evaporated to give a pale yellow oil. Purification by column chromatography on silica, eluting with 0-50% ethyl acetate in hexanes, gave the title compound as a colourless oil (2.26 g) 1H NMR δ (CDCl3): 0.00 (s, 6H), 0.82 (s, 9H), 2.93 (s, 3H), 3.58 (t, 2H), 3.81 (t, 2H), 6.95 (dtd, 1H), 7.16-7.22 (m, 1H) left The phases were separated the aqueous phase was extracted with DCM (3×50 mL) The combined extracts were dried (MgSO4) filtered evaporated to give a pale yellow oil Purification by column chromatography on silica eluting with 0-50% ethyl acetate in hexanes

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

Procedure: 2-(methylamino)ethanol (1.0 g, 13.3 mmol) was stirred in DCM (25.0 ml) under atmosphere of nitrogen. DIEA (3.23 ml, 18.6 mmol) followed by tert-butylchlorodimethylsilane (2.0 g, 13.3 mmol) was added and the reaction mixture was stirred at room temperature over night. The reaction mixture was poured into ether/water. The aqueous layer was extracted with ether three times. The combined organic layer was dried over MgSO4 and evaporated and remaining material was dried under high vacuum to afford title compound (1.4 g, yield: 56%). 1H-NMR (400 MHz, CDCl3) δ 0.08 (s, 6H) 0.91 (s, 9H) 1.93 (br. s., 1H) 2.48 (s, 3H) 2.71 (t, 2H) 3.75 (t, 2H). was added The aqueous layer was extracted with ether three times The combined organic layer was dried over MgSO4 evaporated was dried under high vacuum

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