Water → Bicyclo[2.2.1]heptane-2-carboxylic acid

Temperature

65 °C

Lithium chloride (8.4 mg, 0.20 mmol), para-toluenesulfonic acid (34.4 mg, 0.20 mmol), [(Ph—(R)-Phanephos)Pd2Cl4] (0.01 mmol) and norbornene (94.2 mg, 1 mmol) were weighed into a Biotage 5 ml microwave vial. A stirring bar was added and the vial was sealed with a crimp cap and put under inert atmosphere. Degassed water (between 2.5 equiv. and 15 equiv.), degassed 2-butanone (1.5 ml) and internal standard (approximately 10 μl of 1-methylnaphtalene) were added using a syringe. The solution was mixed before 20 μl of the solution was diluted in CDCl3 and analysed using NMR (to give a t0 spectra that calibrates the internal standard against starting material). The caps were pierced with two needles and quickly placed in an autoclave that had previously been placed under an argon atmosphere before being opened under a flow of argon. The autoclave was sealed, purged three times with CO and then pressurised to 30 bar and heated in a preheated oil bath or heating jacket at 65° C. with constant magnetic stirring. After the desired time, the autoclave was cooled to room temperature and the pressure released slowly. The mixture was then analysed by taking a sample, diluting with CDCl3 and obtaining an 1H NMR spectrum. This shows the formation of the desired acid as a 99:1 mixture of exo and endo isomers (52% conversion to acid, 48% oligomeric dimer-acid) The solvent was carefully removed from the reaction mixture and the residue was purified by column chromatography (SiO2, using hexane: ethylacetate 8:1 as eluent) to give colourless crystals of bicyclo[2.2.1]heptane-2-carboxylic acid (39% isolated yield). The ratio of optical isomers was determined by forming the mandelate ester of the carboxylic acid and calculating the diastereomeric excess by 1H-NMR integration, and in this case was 89:11.

1. additionA stirring bar was added
2. customthe vial was sealed with a crimp
3. customcap
4. additionwere added
5. additionwas diluted in CDCl3
6. customanalysed using NMR (to give a t0 spectra that
7. customThe autoclave was sealed
8. custompurged three times with CO
9. temperatureheated in a preheated oil bath
10. temperatureAfter the desired time, the autoclave was cooled to room temperature
11. additiondiluting with CDCl3
12. customobtaining an 1H NMR spectrum
13. additionas a 99:1 mixture of exo and endo isomers (52% conversion to acid, 48% oligomeric dimer-acid) The solvent
14. customwas carefully removed from the reaction mixture
15. customthe residue was purified by column chromatography (SiO2, using hexane: ethylacetate 8:1 as eluent)

ORD record

ord-a5be90f74c1a43d8a871a12e4ca332b3

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08686183B2