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1 mmol) in dichloromethane (10 mL). The mixture was stirred for 8 h at room
temperature, washed with water (3
) and with aq. sodium hydrogen carbonate
solution (3
), and dried over sodium sulfate. The solvent was removed in vacuo
and the resulting colorless powder was dried under high vacuum; yield 0.74 g
(75%) of 910; IR (KBr): n
max
1770 cm
1
.
ΒΌ
4.3.3.5
Carbonyldiimidazole (CDI)
A simple approach for the resolution of chiral alcohols through a lipase-catalyzed
transesterification of one enantiomer of the corresponding trifluoroethyl carbonate
has been described [658]. (RS)-sec-Phenethyl alcohol
is converted to its 2,2,2-
trifluoroethyl carbonate with CDI in 83% yield.
O
O
OH
O
N
O
O
CF
3
N
CF
3
CH
2
OH
CDI
10 % DMAP
DCM
rt, 24 h
DCM
rt, 2 h
98 %
85 %
913
911
912
Typical procedure. (RS)-sec-Phenethyl 2,2,2-trifluoroethyl carbonate 913 [658]:
(RS)-sec-
Phenethyl-1H-imidazole-1-carboxylate 912: In a dry 250-mL flask, CDI (17.8 g, 110
mmol) was dissolved in dichloromethane (25 mL) with stirring. Further dichloro-
methane (10 mL) was added, followed by a solution of 911 (12.2 g, 100 mmol) in
dichloromethane (10 mL). Upon addition of the alcohol, the solution became light-
yellow and boiled for a few minutes. A yellow precipitate of imidazole could be
seen in the reaction flask after 10 min. After stirring for 4 h at room temperature,
VPC analysis showed that the alcohol had been consumed. The mixture was ex-
tracted with distilled water (3
20 mL) to remove the imidazole, and then dried
(note: if the imidazole is not removed by aqueous extraction, it interferes with the
next reaction). Evaporation of the dichloromethane yielded 21.12 g (98%) of 912 as
a light-yellow oil, which solidified to a brittle white solid on storage in a freezer.
(RS)-sec-Phenethyl 2,2,2-trifluoroethyl carbonate 913: Following the procedure de-
scribed above, CDI (8.9 g, 55 mmol) and 911 (6.1 g, 50 mmol) were used to prepare
912. After extracting with distilled water (3
15 mL) and drying, the solution was
transferred to a new 250 mL flask, and a solution of 2,2,2-trifluoroethanol (12.31 g,
123 mmol) in dichloromethane (10 mL) was added followed by DMAP (0.61 g, 5
mmol). After 20 h at room temperature, VPC analysis showed that the mixture
consisted of
95% carbonate 913. The mixture was then stirred with 0.05 m HCl
(20 mL), and 2.9 m HCl was added dropwise with stirring until pH 2 was reached
(17 mL was required). The phases were separated and the organic phase was ex-
tracted successively with 20 mL portions of 0.05 m HCl, distilled water, saturated
aq. sodium hydrogen carbonate solution, and saturated brine (2
>
20 mL). After
