4-[(dimethylamino)methyl]-2-methylphenol

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of NaH (55-65% disp. in oil, 0.35 g, 8.7 mmol) in dry DMF (10 mL) under nitrogen was cooled by an ice-bath. A solution of 4-[(dimethylamino)methyl]-2-methylphenol—commercially available—(1.1 g, 6.7 mmol) in DMF (5 mL) was added drop-wise over 10 minutes. The mixture was stirred for 30 minutes and then tert-butyl 3-[(methylsulfonyl)oxy]azetidine-1-carboxylate (1.84 g, 7.3 mmol) in DMF (5 mL) was added. The mixture was heated to 80° C. over night and then cooled to RT. Water (100 mL) was added and the mixture was extracted three times with EtOAc (50 mL). The combined organic phases were dried through a phase separator and the solvent was removed by evaporation. The residue was purified by preparative chromatography on a Kromasil C8 column (10 μm 250×20 ID mm) using a gradient of 10-50% acetonitrile in water/acetonitrile/formic acid (95/5/0.2), 100 mL/min. Fractions were collected, pooled and concentrated in vacuo. DCM was added and the solution was filtered through a phase separator and concentrated by evaporation. There was obtained 1.93 g (91%) of 16A as a colourless oil. 1H NMR (500 MHz, CDCl3): δ 1.45 (s, 9H), 2.37 (s, 3H), 2.62 (s, 6H), 3.97 (s, 2H), 3.92-4.04 (m, 2H), 4.24-4.35 (m, 2H), 4.81-4.92 (m, 1H), 6.59 (d, 1H), 6.62 (s, 1H), 7.35 (d, 1H), 8.42 (s, 1H). was cooled by an ice-bath cooled to RT the mixture was extracted three times with EtOAc (50 mL) The combined organic phases were dried through a phase separator the solvent was removed by evaporation The residue was purified by preparative chromatography on a Kromasil C8 column (10 μm 250×20 ID mm) Fractions were collected concentrated in vacuo DCM was added the solution was filtered through a phase separator concentrated by evaporation

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of NaH (55-65% disp. in oil, 0.35 g, 8.7 mmol) in dry DMF (10 mL) under nitrogen was cooled by an ice-bath. A solution of 4-[(dimethylamino)methyl]-2-methylphenol—commercially available—(1.1 g, 6.7 mmol) in DMF (5 mL) was added drop-wise over 10 minutes. The mixture was stirred for 30 minutes and then tert-butyl 3-[(methylsulfonyl)oxy]azetidine-1-carboxylate (1.84 g, 7.3 mmol) in DMF (5 mL) was added. The mixture was heated to 80° C. over night and then cooled to RT. Water (100 mL) was added and the mixture was extracted three times with EtOAc (50 mL). The combined organic phases were dried through a phase separator and the solvent was removed by evaporation. The residue was purified by preparative chromatography on a Kromasil C8 column (10 μm 250×20 ID mm) using a gradient of 10-50% acetonitrile in water/acetonitrile/formic acid (95/5/0.2), 100 mL/min. Fractions were collected, pooled and concentrated in vacuo. DCM was added and the solution was filtered through a phase separator and concentrated by evaporation. There was obtained 1.93 g (91%) of 16A as a colourless oil. 1H NMR (500 MHz, CDCl3): δ 1.45 (s, 9H), 2.37 (s, 3H), 2.62 (s, 6H), 3.97 (s, 2H), 3.92-4.04 (m, 2H), 4.24-4.35 (m, 2H), 4.81-4.92 (m, 1H), 6.59 (d, 1H), 6.62 (s, 1H), 7.35 (d, 1H), 8.42 (s, 1H). was cooled by an ice-bath cooled to RT the mixture was extracted three times with EtOAc (50 mL) The combined organic phases were dried through a phase separator the solvent was removed by evaporation The residue was purified by preparative chromatography on a Kromasil C8 column (10 μm 250×20 ID mm) Fractions were collected concentrated in vacuo DCM was added the solution was filtered through a phase separator concentrated by evaporation

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of NaH (55-65% disp. in oil, 0.35 g, 8.7 mmol) in dry DMF (10 mL) under nitrogen was cooled by an ice-bath. A solution of 4-[(dimethylamino)methyl]-2-methylphenol—commercially available—(1.1 g, 6.7 mmol) in DMF (5 mL) was added drop-wise over 10 minutes. The mixture was stirred for 30 minutes and then tert-butyl 3-[(methylsulfonyl)oxy]azetidine-1-carboxylate (1.84 g, 7.3 mmol) in DMF (5 mL) was added. The mixture was heated to 80° C. over night and then cooled to RT. Water (100 mL) was added and the mixture was extracted three times with EtOAc (50 mL). The combined organic phases were dried through a phase separator and the solvent was removed by evaporation. The residue was purified by preparative chromatography on a Kromasil C8 column (10 μm 250×20 ID mm) using a gradient of 10-50% acetonitrile in water/acetonitrile/formic acid (95/5/0.2), 100 mL/min. Fractions were collected, pooled and concentrated in vacuo. DCM was added and the solution was filtered through a phase separator and concentrated by evaporation. There was obtained 1.93 g (91%) of 16A as a colourless oil. 1H NMR (500 MHz, CDCl3): δ 1.45 (s, 9H), 2.37 (s, 3H), 2.62 (s, 6H), 3.97 (s, 2H), 3.92-4.04 (m, 2H), 4.24-4.35 (m, 2H), 4.81-4.92 (m, 1H), 6.59 (d, 1H), 6.62 (s, 1H), 7.35 (d, 1H), 8.42 (s, 1H). was cooled by an ice-bath cooled to RT the mixture was extracted three times with EtOAc (50 mL) The combined organic phases were dried through a phase separator the solvent was removed by evaporation The residue was purified by preparative chromatography on a Kromasil C8 column (10 μm 250×20 ID mm) Fractions were collected concentrated in vacuo DCM was added the solution was filtered through a phase separator concentrated by evaporation