The synthetic process of N-(3,3-Dimethoxy-1-trifluoromethyl-propyl)-acetamide contains 5 steps. The synthetic routes are as follows:

A. N-(2,2,2-Trifluoro-1-hydroxyethyl)-acetamide (1). A 250-mL, two-necked, round-bottomed flask, equipped with a magnetic stir bar and fitted with a glass stopper and a condenser, is charged with 2,2,2-trifluoro-1-methoxyethanol (14.75 g, 102 mmol), acetamide (6.0 g, 102 mmol) and 1,4-dioxane (100 mL). The resulting solution is heated to reflux and stirred in an oil bath under argon for 2 h. The reaction mixture is then cooled to ambient temperature and transferred to a single-necked flask. The solvent is evaporated under reduced pressure and the residue dried under vacuum (25 °C, 1 mmHg) for 1 h to give 16.8 g of a colorless solid residue. This product is dissolved in tert-butyl methyl ether (20 mL) in a one-necked, round-bottomed flask. (10 g) is added to the solution and the solvent is evaporated under reduced pressure. The resulting adsorbate is added on top of a silica gel column (approximately 180 g), which is eluted with hexanes/ethyl acetate (3:2). The fractions containing the product are combined and evaporated to give N-(2,2,2-trifluoro-1-hydroxyethyl)acetamide (1) as a colorless solid (8.98 g, 56%).

B. N-1-(Chloro-2,2,2-trifluoro-ethyl)acetamide (2). A 250-mL, two-necked, round-bottomed flask is equipped with a magnetic stir bar and fitted with a glass stopper and a condenser. The top of the condenser is fitted with a T-joint allowing argon to sweep the effluent gases (HCl and sulfur dioxide) from the reaction into the exit duct of a well ventilated fume hood. The flask is charged with compound 1 (8.98 g, 57 mmol), chloride (7.1 g, 60 mmol) and heptane (65 mL). The resulting suspension is stirred and heated to 85 °C in an oil bath under argon until a clear solution has formed. Stirring is continued for 15 min before the mixture is allowed to cool to ambient temperature, whereupon the product starts to crystallize. After standing for 30 min, the crystals are collected by filtration, rinsed with heptane (2 × 25 mL) and dried under vacuum (25 °C, 1 mmHg) for 1 h to provide product 2 (9.3 g, 93%) as colorless crystals, which were used without further purification in the next step.

C. S-(1-Acetylamino-2,2,2-trifluoroethyl) O-ethyl dithiocarbonate (3). A 500-mL, one-necked, round-bottomed flask, equipped with a magnetic stir bar, is charged with N-(1-chloro-2,2,2-trifluoro-ethyl)acetamide 2 (9.2 g, 52 mmol) and EtOH (100 mL). O-ethyl xanthate (9.2 g, 57 mmol) is added in portions over a period of 5 min. The resulting mixture is stirred at ambient temperature for 15 min  before the reaction is quenched with water (100 mL). The solution is extracted with ether/hexanes solution (7:3, 3 × 150 mL), the combined organic layers are dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure to provide a solid residue which is dried under vacuum (25 °C, 1 mmHg) for 1 h to give xanthate 3 (12.5 g, 91%) as a white solid.

D. 3-Acetylamino-1-ethoxythiocarbonylsulfanyl-4,4,4-trifluorobutyl acetate (4). A flame-dried, 100-mL, two-necked, round-bottomed flask is fitted with magnetic stir bar, a glass stopper and a condenser connected to the argon line. The flask is charged with xanthate 3 (12.4 g, 47.5 mmol), vinyl acetate (5.1 mL, 54.6 mmol) and 1,2-dichloroethane (50 mL) and the resulting solution is heated under reflux in an oil bath for 15 min under argon. Four equal portions of lauroyl peroxide (473 mg each, 1.9 g overall, 10 mol%) are added in intervals of 1.5 h to the refluxing solution. After 7 h under reflux, the solution is allowed to reach ambient temperature before the solvent is evaporated under reduced pressure to give adduct 4 as a pale yellow oil (17.8 g), which was used in the next step without further purification.

E. N-(3,3-Dimethoxy-1-trifluoromethyl-propyl)-acetamide (5). A flame-dried, 250-mL, two-necked, round-bottomed flask is fitted with a large magnetic stir bar, a glass stopper and a reflux condenser connected to the argon line. The flask is charged with the crude radical adduct 4 (17.8 g), MeOH (100 mL) and (±)-10-camphorsulfonic acid (12.5 mol%, 1.37 g, 5.9 mmol). The mixture is refluxed in an oil bath for 24 h before it is cooled to ambient temperature. The solvent is evaporated under reduced pressure. The residue is dissolved in ethyl acetate (80 mL) and the organic phase is washed successively with saturated aqueous sodium bicarbonate (20 mL) and saturated aqueous sodium chloride (20 mL). The organic solvent is dried over MgSO₄, filtered, and evaporated under reduced pressure. The resulting brown syrup (11.8 g) is purified by flash chromatography on silica gel using hexanes/ethyl acetate (2:3) as the eluent to give N-(3,3-dimethoxy-1-trifluoromethyl-propyl)-acetamide (5) as colorless crystals (4.43 g, 41%).