Triethylamine → HCID 178525703, compound

To a solution of cis/trans-ethyl 4-(chloro(hydroxyimino)methyl)cyclohexanecarboxylate (1.20 g, 5.13 mmol) and 1-morpholinocyclohexene (1.72 g, 10.3 mmol) in dichloromethane (50 ml) was added triethylamine (0.72 ml, 5.1 mmol) at 0-5° C. The cooling bath was removed 30 minutes after completed addition. After stirring for 4 h the solvent was evaporated. The residue was redissolved in 6 M aqueous hydrochloric acid solution (50 ml), and the mixture was and heated at reflux for 1 h. After cooling to room temperature the reaction mixture was partitioned between crushed ice (100 g) and ethyl acetate (50 ml). The layers were separated. The aqueous layer was extracted with two 50-ml portions of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. Purification with n-heptane/ethyl acetate as eluent gave cis-4-(4,5,6,7-tetrahydro-benzo[d]isoxazol-3-yl)-cyclohexanecarboxylic acid (0.40 g, 31%) as white solid (MS m/e: 248 ([M−H]−)) and trans-4-(4,5,6,7-tetrahydro-benzo[d]isoxazol-3-yl)-cyclohexanecarboxylic acid (0.09 g, 7%) as white solid (MS m/e: 248 ([M−H]−)).

1. customThe cooling bath was removed 30 minutes
2. additionaddition
3. customwas evaporated
4. dissolutionThe residue was redissolved in 6 M aqueous hydrochloric acid solution (50 ml)
5. temperatureheated
6. temperatureat reflux for 1 h
7. customwas partitioned
8. custombetween crushed ice (100 g) and ethyl acetate (50 ml)
9. customThe layers were separated
10. extractionThe aqueous layer was extracted with two 50-ml portions of ethyl acetate
11. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
12. concentrationconcentrated in vacuo
13. customPurification with n-heptane/ethyl acetate as eluent

ORD record

ord-596da6fae15b49019eb4c7182ceac9c6

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08513238B2