Methyl (1R,5R)-5-hydroxy-2--1-acetate (CAS no.: 49825-99-2), which is also known as 2-Cyclopentene-1-acetic acid, 5-hydroxy-, , (1R-trans)-, could be produced as the following synthetic routes.

A. Pyrolysis of di to form cyclopentadiene. Cyclopentadiene is prepared from its dimeric form by distillation according to the method of Moffett. The apparatus for the distillation is assembled as shown in Figure 1. The equipment consists of a 250-mL flask, a Friedrichs condenser fitted with a Haake Model FE hot water circulator, a Claisen head, a thermometer, a gas inlet tube, and a collection receiver that is cooled to -78°C in a dry ice–acetone bath.

In the 250-mL flask is placed 100 mL of dicyclopentadiene. The material is heated at reflux (bath temperature 200–210°C) under a nitrogen atmosphere. After a 5-mL forerun is collected and discarded, the collection receiver is cooled to -78°C and 25 mL (0.30 mol) of cyclopentadiene is rapidly distilled at bp 36–42°C. A slight positive pressure of nitrogen is maintained throughout the distillation to prevent moisture from entering the system. The distilled cyclopentadiene is stored at -78°C until it is used. Residual dicyclopentadiene can be reused until it solidifies on cooling.

B. Preparation in situ of methyl 2,4-cyclopentadiene-1-acetate. Cyclopentadienylsodium is prepared by modification of the methods of King and Hafner.

In a 500-mL, three-necked Morton flask fitted with a condenser, mechanical stirrer, and gas inlet tube is placed 8.6 g (0.375 g-atom) of sodium and 75 mL of dry xylene; the unstirred mixture is heated at reflux under a nitrogen atmosphere. After the xylene has reached its boiling point and the sodium has melted, the solution is rapidly stirred to produce a very fine-grained sodium sand. Quickly the heating mantle is removed and stirring stopped. After cooling, the xylene is pipetted or siphoned away from the sodium sand and stored for future use.

The sand is washed with 3 × 25 mL of dry tetrahydrofuran and then is layered with 100 mL of dry tetrahydrofuran, and the mixture is cooled to -10°C under a nitrogen atmosphere. A solution of 25 mL (0.30 mol) of cyclopentadiene in 25 mL of tetrahydrofuran is added dropwise using a dropping funnel. After the addition is complete, the mixture is stirred overnight at room temperature, by which time hydrogen evolution has ceased. In the absence of air, the solution ranges from near colorless to bright pink.

In a 1-L, three-necked flask fitted with a 200-mL pressure-equalizing dropping funnel, mechanical stirrer, and a gas inlet tube is placed 45.9 g (0.30 mol) of methyl bromoacetate and 75 mL of tetrahydrofuran and the mixture is cooled to -78°C in an inert atmosphere.

The solution of ca. 0.30 mol of cyclopentadienylsodium is decanted from residual sodium sand with a U-tube into the dropping funnel and is added dropwise over a 2-hr period. A white precipitate of sodium bromide forms during the addition. The heterogeneous solution is stirred overnight at -78°C to ensure complete formation of methyl 2,4-cyclopentadiene-1-acetate.

C. Asymmetric hydroboration with ( + )-di-3-pinanylborane to form methyl (1R,5R)-5-hydroxy-2-cyclopentene-1-acetate. The ( + )-di-3-pinanylborane is prepared from ( - )-α-pinene by a modification of the method of Brown.

In a 2-L, three-necked flask fitted with a condenser, mechanical stirrer, and a gas inlet tube is placed 90.0 g (0.66 mol) of ( - )-α-pinene. The flask is cooled to 0°C and under an inert atmosphere a total of 300 mL (0.30 mol) of 1 M borane in tetrahydrofuran is added dropwise over a 1-hr period. The solution is stirred for 18 hr at 0°C, during which time a white precipitate of ( + )-di-3-pinanylborane forms. This solution is then cooled to -78°C. The ca. 0.30 mol solution of methyl 2,4-cyclo-pentadiene-1-acetate (Section B) is transferred at -78°C to a 500-mL pressure-equalizing dropping funnel through a U-tube in an inert atmosphere and is added rapidly, in one portion, to the stirring solution of di-3-pinanylborane at -78°C. After this mixture is stirred for 6 hr at -78°C, the bath temperature is allowed to rise to 0°C and the mixture is stirred for 16 hr at 0°C to complete the hydroboration reaction.

To the reaction mixture is added dropwise 90 mL of 3 N aqueous sodium hydroxide, followed by 90 mL of 30% hydrogen peroxide. The mixture is stirred for 30 min to complete the oxidation process. A total of 3 g of sodium bisulfite, 5 g of sodium chloride, and 125 mL of ether are added and the mixture is stirred for 10 min. On standing, the reaction mixture separates into two layers, which are separated with a 1-L separatory funnel. The organic layer is washed with brine (2 × 50 mL). The water layer and the brine washes are combined and extracted with ether (3 × 125 mL). All the organic layers are then combined and dried over anhydrous magnesium sulfate. Filtration and removal of solvent under reduced pressure yield 110 g of a pale-yellow oil containing the desired product as well as ( + )-isopinocampheol, and ( - )-α-pinene. The product mixture is dissolved in 250 mL of ether and is extracted with 1 M aqueous silver nitrate solution (3 × 100 mL). The aqueous layers are combined and back-extracted once with 50 mL of ether. The ether layers containing ( + )-isopinocampheol are discarded.

The aqueous layers containing the silver(I) complex of methyl (1R,5R)-5-hydroxy-2-cyclopentene-1-acetate are then treated with an excess of saturated brine to precipitate silver chloride and free the desired product. After precipitation is complete, the water layer is decanted from the solid silver chloride. The solids are washed with ether (4 × 100 mL) and each ether layer is used to extract the water layer. The combined ether layers are washed with 50 mL of brine and dried over anhydrous magnesium sulfate. Filtration and removal of solvent under reduced pressure yield 16–19 g of crude product. The product is distilled through a 4-in.-Vigreux column at 0.1 mm pressure to yield 12.8–14.7 g (27–31%) of methyl (1R,5R)-5-hydroxy-2-cyclopentene-1-acetate, bp 74–78°C at 0.1 mm, [α]_D²⁵ -132° (CH₃OH, c 1.06)