Hexadecanoic acid, 16-bromo-, 1,1-dimethylethyl ester synthesis

Yield:865200-89-1 85%

Reaction Conditions:

Stage #1: 16-bromohexadecanoic acidwith trifluoroacetic anhydride in tetrahydrofuran at 0; for 0.5 h;
Stage #2: tert-butyl alcohol in tetrahydrofuran at 20; for 2 h;

Steps:

1 Synthesis of f-butyl 16-bromohexadecanoate (6)

16-bromohexadecanoic acid (2) (0.091 g, 0.27 mmol) was dissolved in anhydrous THF (1 ml.) and cooled to 0 °C before trifluoroacetic anhydride (0.085 ml_, 0.60 mmol) was added slowly. After 30mins of stirring, 5 ml. of f-BuOH was added all at once and the mixture was stirred at room temperature for 2h. The reaction was then quenched with saturated NaHC0₃solution and the aqueous layer was then extracted twice with CH₂CI₂. The organic layer was separated from the aqueous layer and dried with brine and Na₂S0₄. The solvent was then evaporated under reduced pressure and purified by flash chromatography (3% ethyl acetate/hexane) to give a clear oil of 3 (85%).¹H NMR (400 MHz, CDCI₃) d 3.40 (t, J = 6.9 Hz, 2H), 2.19 (t, J = 7.5 Hz, 2H), 1 .90 - 1 .80 (quint, J= 7.1 Hz, 2H), 1 .63 - 1.51 (m, 2H), 1.47 - 1 .35 (m, 1 1 H), 1.26 (d, J = 8.4 Hz, 20H).¹³C NMR (101 MHz, CDCI₃) d 173.49, 80.01 , 77.48, 77.16, 76.84, 35.79, 34.14, 33.00, 29.77, 29.68, 29.62, 29.58, 29.45, 29.25, 28.91 , 28.33, 28.28, 25.27.

References:

WO2020/180249,2020,A1 Location in patent:Page/Page column 26; 30; 31-33