3,3-difluorobutan-1-ol synthesis

Yield:858359-36-1 88%

Reaction Conditions:

with lithium aluminium tetrahydride in tetrahydrofuran at 0 - 20;

Steps:

6.6.1 6.1 Synthesis of 3,3-difluorobutan-1-ol XXIII

To a solution of ethyl 3,3-difluorobutanoate (1.0 eq., 10 g, 65.7 mmol) in anhydrous THF (330 mL) at 0°C was added lithium aluminium hydride (2.2 eq., 72 ml_, 144.6 mmol).The reaction mixture was stirred at 0°C during 2 h and at room temperature overnight. To the cooled solution (0°C) was added a mixture of Glaubler's Salt (IS^SC I OhbO and Celite) and water until hydrogen release was no longer evident. An additional quantity of Glaubler's reactant was added and the mixture was stirred at room temperature during 30 min. The mixture was then filtered and the filtrate was evaporated to dryness (bath temperature: max 20°C) to give 3,3-difluorobutan-1-ol XXIII (8.8 g, 58 mmol) as pale yellow oil. Yield: 88%
¹H NMR (400 MHz, DMSO-c/₆): δ 6.95 (t, J = 5.1 Hz, 1 H), 5.91 - 5.82 (m, 4H), 4.32 (tt, J = 15.9, 6.8 Hz, 2H), 4.10 - 4.02 (m, 2H), 3.90 (t, J = 19.3 Hz, 3H).

References:

WO2019/11767,2019,A1 Location in patent:Page/Page column 43