Organic Syntheses, CV 7, 221
Submitted by Andrew S. Kende and Pawel Fludzinski
1.
Checked by Cynthia McClure and Edwin Vedejs.
1. Procedure
A dry,
2-L, one-necked, round-bottomed flask is equipped with a
1-L pressure-equalizing funnel and a
large magnetic stirring bar. The system is flame-dried under an internal atmosphere of dry
nitrogen (Note
1). The flask is charged with
300 mL of anhydrous tetrahydrofuran (Note
2) and
100 g of monoethyl fumarate. The solution is then stirred under
nitrogen and brought to about −5°C using an
ice–salt/methanol bath (−10°C) (Note
3). A
1 M solution of 700 mL (0.70 mol) of borane–tetrahydrofuran complex (Note
4) is
cautiously added dropwise (rapid
H2 evolution occurs) with rigorous temperature control to avoid an exothermic reaction. The ice–salt bath is maintained in position throughout the 90 min of addition. The stirred reaction mixture is then gradually allowed to warm to room temperature over the next 8–10 hr. The reaction is carefully quenched at room temperature by dropwise addition of 1 : 1 water :
acetic acid (ca. 20 mL) with stirring until no more gas evolution occurs. The reaction is concentrated at room temperature and water pump pressure to a slurry by removal of most of the
tetrahydrofuran. The slurry is carefully poured over a 20-min period into
300 mL of ice-cold, saturated sodium bicarbonate solution with mechanical stirring to avoid precipitation of solids, and the product is extracted with
300 mL of ethyl acetate. The aqueous layer is again extracted with
100 mL of ethyl acetate. The organic layers are combined, washed once with
200 mL of saturated sodium bicarbonate, then dried well with anhydrous
magnesium sulfate.
An analytical sample may be prepared by quick distillation (or Kugelrohr distillation) at 117–120°C (15 mm), but there is significant loss of material because of decomposition in the distillation pot. From 1 g of product, 0.72 g of pure material is obtained in this way, and recovery decreases as scale of distillation increases.
2. Notes
1. This is accomplished by passing a stream of dry
nitrogen through the reaction vessel. During the reaction, a slight positive pressure of
nitrogen is maintained throughout the apparatus.
3. The flask is cooled with the ice–salt/methanol bath for 30 min before the next addition to insure complete cooling of the solution.
4.
Borane-tetrahydrofuran is commercially available from Aldrich Chemical Company, Inc. When a fresh bottle is used, titration is not necessary.
5.
1H NMR data for ethyl 4-hydroxycrotonate are as follows (100 MHz, CDCl
3): δ 1.30 (t, 3 H,
J = 7), 3.58 (br s, 1 H), 4.17 (q, 2 H,
J = 7), 4.30 (m, 2 H), 6.03 (dt, 1 H,
J = 16), 6.98 (dt, 1 H,
J = 16).
3. Discussion
Ethyl (or methyl) 4-hydroxycrotonate has previously been prepared in
51% yield by silver oxide-assisted solvolysis of
methyl 4-bromocrotonate,
3 or in
94% yield by reaction of
glycolaldehyde with
(carbomethoxymethylene)triphenylphosphorane.
4 Both procedures require very expensive starting materials or reagents. Several multistep procedures for preparing the title compound have also been reported.
5 6 7 8 The procedure described above represents a convenient one-step alternative for preparing
ethyl 4-hydroxycrotonate, requiring inexpensive starting materials and reagents. This procedure relies on the selective reduction of a carboxylic acid in the presence of a carboxylic ester with
borane, which is well documented.
9
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