Acetic Acid → HCID 178501136, compound

To a solution of N,N-diisopropylamine (1.59 ml, 11.2 mmol) in dry tetrahydrofuran (10 ml) was added 1.6 M n-butyl lithium in n-hexane (7.00 ml, 11.2 mmol) at 0-5° C. Addition of N′-cyclohexylidene-N,N-dimethyl-hydrazine (1.50 g, 10.7 mmol) after 15 minutes was followed by stirring for 90 minutes. The resulting solution was cannulated dropwise to a solution of trans-4-chlorocarbonyl-cyclohexanecarboxylic acid methyl ester (2.19 g, 10.7 mmol) in dry tetrahydrofuran (50 ml) at −65° C. The reaction mixture was stirred for 20 h at −78° C. The cooling bath was removed and the reaction mixture was quenched by addition of acetic acid (0.65 ml, 11 mmol) at −5° C. The mixture was partitioned between ethyl acetate (150 ml) and saturated ammonium chloride solution (100 ml). The layers were separated. The aqueous layer was extracted with one 100-ml portion of ethyl acetate. The combined organic layers were washed with one 50-ml portion of brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification with n-heptane/ethyl acetate as eluent gave the title compound (0.98 g, 30%) as light yellow oil with a purity of 60%. MS m/e: 309 ([M+H]+)

1. stirringThe reaction mixture was stirred for 20 h at −78° C
2. customThe cooling bath was removed
3. customThe mixture was partitioned between ethyl acetate (150 ml) and saturated ammonium chloride solution (100 ml)
4. customThe layers were separated
5. extractionThe aqueous layer was extracted with one 100-ml portion of ethyl acetate
6. washThe combined organic layers were washed with one 50-ml portion of brine
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationconcentrated in vacuo
9. customPurification with n-heptane/ethyl acetate as eluent

ORD record

ord-759066c0e0874a578af1f1f0f52e9d8f

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346824B2