实验操作A 30 L doublejacketed glass-lined steel reactor was charged with amide 35
(2.39 kg, 4.31 mol, 1.00 equiv) and toluene (11.9 L, 5 vol.).
The resulting mixture was heated to IT = 90−100 °C. DEANB
(1.41 kg, 8.63 mol, 2.00 equiv) was added over 35 min at IT =
90−100 °C, resulting in moderate gas evolution. The resulting
reaction mixture was stirred at IT = 90−100 °C for 22 h before
a second portion of DEANB (703 g, 4.31 mmol, 1.00 equiv)
was added over 15 min at IT = 90−100 °C. Stirring was
continued at this temperature for 6 h before a third portion of
DEANB (703 g, 4.31 mmol, 1.00 equiv) was added over 15
min at IT = 90−100 °C, and the reaction mixture was stirred at
this temperature for 15 h (98% conversion of 35). A fourth
portion of DEANB (352 g, 2.16 mol, 0.500 equiv) was added
over 15 min at IT = 90−100 °C and stirring was continued at this temperature for 2 h (>99% conversion of 35).
MeOH
(2.09 L, 51.8 mol, 12.0 equiv) was added over 40 min at IT =
90−100 °C resulting in strong gas evolution (dilute with
strong N2-flow!). The reaction mixture was kept for 1 h at this
temperature before the distillation of 2 L (0.8 vol.) of a mixture
of MeOH and B(OMe)3 was performed. Then, 2 M aq. HCl
solution (12 L, 5 vol.) was added over 25 min at ET = 95 °C
and stirring was continued at this temperature for 1 h, resulting
in the distillation of 1.5 L (0.6 vol.) of solvent. The resulting
suspension was then cooled to IT = 0−10 °C and aged at this
temperature for 1 h. An IPC confirmed the absence of residual
borane complexes, and the pH of the mixture was measured to
be 1. The solid was collected by filtration and washed with
toluene (7.2 L, 3 vol.) and water (7.2 L, 3 vol.), and dried with
a N2-stream. The wet solid was loaded back into the reactor,
and iPrOAc (12 L, 5 vol.) was added at IT = 20−30 °C,
followed by 1 M aq. NaOH solution (12 L, 5 vol.). The
resulting mixture was stirred at IT = 20−30 °C for 40 min until
all the solids were dissolved. The phases were separated, and
the aqueous phase was discarded. The organic phase was
washed once with water (12 L, 5 vol.) before it was
concentrated to dryness by rotavap at ET = 50 °C under
reduced pressure (160−20 mbar) to afford 27 (2.35 kg, 4.35
mol, quantitative yield) as a yellow oil. 参考文献 https://doi.org/10.1021/acs.oprd.3c00492
