Cl.[NH2:2][CH:3]([CH:10]([CH3:12])[CH3:11])[CH:4]([OH:9])[C:5]([F:8])([F:7])[F:6].CN1CCOCC1.[Cl:20][CH2:21][C:22](Cl)=[O:23]>O1CCCC1.C(OCC)(=O)C>[Cl:20][CH2:21][C:22]([NH:2][CH:3]([CH:10]([CH3:12])[CH3:11])[CH:4]([OH:9])[C:5]([F:6])([F:7])[F:8])=[O:23]To a solution of 3-amino-1,1,1-trifluoro-4-methyl-2-pentanol hydrochloride (20 g) in distilled tetrahydrofuran (480 mL) under nitrogen was added 4-methylmorpholine (21.8 mL) resulting in a white precipitate. A solution of chloroacetyl chloride (7.7 mL) in distilled tetrahydrofuran (40 mL) was added dropwise over 1 hour, and the mixture was stirred overnight. The mixture was diluted with ethyl acetate and filtered to remove undissolved solids. The filtrate was washed with 10% hydrochloric acid, water, saturated aqueous sodium bicarbonate and brine. The solid that had been filtered was dissolved in water, the aqueous phase was extracted with ethyl acetate (twice), and the extracts were washed as the first extract had been. The organic phases were combined, dried, and evaporated to give 2-chloro-N-(3,3,3-trifluoro-2-hydroxy-1-isopropyl-propyl)acetamide as an oil (23.8 g); TLC: Rf =0.70, dichloromethane:methanol (95:5); MS: m/z=248(M+1 for 35Cl).
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