Water → (+-)-Penicillamine

A solution of the boronate ester-substituted alkene (50.7 mg) was photooxygenated in 10 mL of CD3OD containing 50.3 mg of polymer-bound Rose Bengal in an ice bath for 20 min. Oxygen gas was bubbled through the solution while it was irradiated with 1000 W Na lamp through a Kapton optical cutoff filter. The beads were filtered off, the solvent was evaporated and the residue stored at −20° C. 1H NMR (CDC3) δ 0.91 (d, 6H), 1.24 (d, 6H), 1.38 (s, 12H), 2.29-2.41 (m, 2H), 3.17 (s, 3H), 7.19-7.23 (dd, 1H), 7.32 (d, 1H), 7.55 (d, 1H). Dioxetane 12 is prepared by a process analogous to the one described in example 1. The known compound 3-bromo-4-chlorobenzoic acid is esterified in 2,2,2-trifluorethanol with acid catalysis to prepare the trifluoroethyl ester. Adamantanone and 2,2,2-trifluorethyl 3-bromo-4-chloro-benzoate are coupled with the reagent prepared from TiCl3 and LiAlH4. The bromoalkene is converted to the boronic acid alkene by reaction with B(Oi-Pr)3 and n-BuLi in THF followed by hydrolysis. The boronic acid alkene is photooxygenated by irradiation with a Na lamp under a stream of O2 with methylene blue sensitizer to yield dioxetane 12. Dioxetane 13 is prepared by a process analogous to that disclosed in EP 0779293A1 depicted below. Briefly, 3-bromobenzoic acid is esterified with 2,2,4,4-tetramethyl-1,3-propanediol to produce the ester (i). The alcohol function is oxidized with pyridinium chlorochromate (PCC) to form (ii). Reductive coupling of the ketone and ester groups with TiCl3/LiAlH4 produces the cyclic vinyl ether (iii). Conversion to the boronic acid is done with triisopropyl borate, followed by hydrolysis as described above. The double bond is photooxygenated as above to produce dioxetane 13. Dioxetane 14 is prepared by a process analogous to the one described in example 1. The known ketone tricyclo[7.3.2.02,7]tridec-2,7-ene-13-one (U.S. Pat. No. 6,461,876) and methyl 4-chloro-3-bromobenzoate are coupled with the reagent prepared from TiCl3 and LiAlH4. The bromoalkene is converted to the boronic acid alkene by reaction with B(Oi-Pr)3 and n-BuLi in THF followed by hydrolysis. The boronic acid alkene is photooxygenated by irradiation with a Na lamp under a stream of O2 with methylene blue sensitizer to yield dioxetane 14. Dioxetane 15 is prepared by a process analogous to the one described in example 1. The known compound 3-bromo-4-chlorobenzoic acid is esterified in 2,2,2-trifluorethanol with acid catalysis to prepare the trifluoroethyl ester. Adamantanone and 2,2,2-trifluorethyl 3-bromo-4-chlorobenzoate are coupled with the reagent prepared from TiCl3 and LiAlH4. The bromoalkene is converted to the boronic acid alkene by reaction with B(Oi-Pr)3 and n-BuLi in THF followed by hydrolysis. The boronic acid alkene is photooxygenated by irradiation with a Na lamp under a stream of O2 with methylene blue sensitizer to yield dioxetane 15. 22. Synthesis of Benzothiazoleboronic Acid Derivatives as Signalling Compounds for Luminescent Detection. A solution of 1.0 g of compound 2c and 620 mg of DL-penicillamine was prepared in 30 mL. THF. To this was added 2.0 mL of triethylamine was added followed by 3.0 mL of water. The solution was stirred for 1 h while being sparged with Ar. The solvent was evaporated, the residue taken up in CH2Cl2 and the solution dried on MgSO4. Evaporation of the solvent yielded the triethylamine salt of 15a. The free acid was liberated by taking the residue up in CH2Cl2, and washing the solution with 5% aq. citric-acid followed by water, drying on MgSO4 and evaporation of solvent. Compound 15a was obtained 1.34 mg, 92% yield. 1H NMR (CDCl3) δ 1.379 (s, 12H), 1.581 (s, 3H). 1.910 (s, 3H), 4.970 (s, 1H), 7.957 (d, 1H), 8.140 (d, 1H), 8.432 (s, 1H).

1. additionwas added
2. customwhile being sparged with Ar
3. customThe solvent was evaporated
4. customthe solution dried on MgSO4
5. customEvaporation of the solvent
6. customyielded the triethylamine salt of 15a

ORD record

ord-82483cd7e91b46dea5860de3acf4ff05

Source dataset

uspto-grants-2005_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06919463B2