3-chloro-N-methylpropan-1-amine

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 N-[(2R)-2-methoxycarbonyl-2-trifluoromethanesulfonyloxyethyl]-N-[4-(4-trifluoromethylphenoxy)phenyl]methanesulfonamide (565 mg, 1.0 mmol) from Step C in dried CH2Cl2 (2 mL) at 0° C. under N2 was added N-methyl-3-chloropropyl-amine (ca. 1.0 M in CH2Cl2, 4.0 mL, 4.0 mmol) dropwise. The mixture was allowed to warm to room temperature and was stirred for 1 h. The mixture was directly concentrated to give a crude mixture, which was purified by silica gel chromatography using EtOAc/hexane (1/4 to 1/1) as the eluent to give 455 mg of the product (81%) as a sticky oil. 1H NMR (300 MHz, CDCl3) δ 7.62 (d, J=9.0 Hz, 2H), 7.35 (d, J=9.0 Hz, 2H), 7.12-7.04 (m, 4H), 3.96-3.90 (m, 2H), 3.69 (s, 3H), 3.59-3.54 (m, 2H), 3.47 (t, J=7.5 Hz, 1H), 2.94 (s, 3H), 2.75-2.55 (m 2H), 2.27 (s, 3H), 1.90-1.83 (m, 2H); MS (EI) 522 (M++1, 100). The mixture was directly concentrated to give a crude mixture, which was purified by silica gel chromatography

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

Procedure: 0.8 mL of 37% aqueous formaldehyde solution is added to suspension of 3-chloro-N-methylpropan-1-amine (1.4 g or 1.3 mmol) in dioxane (30 mL), the resulting mixture is slightly heated until it becomes a solution. The solution is cooled to room temperature, 1.6 mL of diethyl phosphate is added thereto, stirring at room temperature for 30 min, and then stirring at 90-100° C. for 3 h, the reaction is completed. The solvent is removed under reduced pressure, and the residue is purified by column chromatography (eluent: 1-4% MeOH in DCM) to obtain 2.3 g target compound (yield: 81%). The analytical data of the obtained product are as follows: 1HNMR (400 MHz, CDCl3): δ=4.17-4.10 (m, 4H), 3.74-3.53 (m, 4H), 3.28-3.08 (m, 2H), 2.80 (s, 3H), 2.25-2.09 (m, 2H), 1.29 (t, J=6.8 Hz, 6H). the resulting mixture is slightly heated until it stirring at 90-100° C. for 3 h The solvent is removed under reduced pressure the residue is purified by column chromatography (eluent: 1-4% MeOH in DCM)