Concentration organic residues from water supplies

High-Performance Concentration System for the Isolation of Organic Residues from Water Supplies... 

The product from Step 1 (13.4 mmol) was dissolved in 100 ml apiece THE and a saturated solution of NH4CI, placed in a water bath, and activated zinc dust (230 mmol) added. The mixture stirred 20 minutes and was then filtered through a pad of diatomaceous earth. The organic layer was separated and the aqueous layer extracted with 20 ml THF. The organic phase was washed with brine, dried, and concentrated. The residue was triturated with 20 ml water and the product isolated in 71% yield as a tan solid. NMR data supplied. 

The product from Step 1 (6.25 mmol) was dissolved in 32 ml ethylene glycol dimethylether, cooled to -10°C, POCI3 (16.3mmol) added followed by the dropwise addition of triethylamine (32.6 mmol) dissolved in 3 ml ethylene glycol dimethylether, and the reaction temperature kept below —5°C. The mixture was gradually warmed to ambient temperature over 1 hour, quenched with water, and extracted with EtOAc. The organic phase was washed with saturated aqueous NaHCOj, dried, and concentrated. The residue was triturated with petroleum ether, filtered, and the product isolated in 90% yield. NMR data supplied. 

O-Methylhydroxylamine hydrochloride (0.4mol) and lOg 3A molecular sieves were added to a solution of the product from Step 1 (0.1 mol) dissolved in 50 ml methyl alcohol and the mixture stood at ambient temperature 16 hours. The solution was concentrated, the residue partitioned between methyl t-butyl ether and water, the organic phase washed, dried, concentrated and the product isolated in 100% yield as 1 1 E/Z isomer mixture. H-NMR data supplied. (Note 3)... 

The product from Step 1 (35.0mmol) was dissolved in 100 mlTHF,borane THF(52.5 mmol) added over 90 minutes, the mixture stirred 30 minutes under ice cooling, and then 4 hours at ambient temperature. Thereafter, 5 ml ethyl alcohol was added, the mixture stirred 5 minutes, followed by the addition of 13 ml 6M borane THF. The mixture was stirred 20 minutes under ice cooling, 3 hours at ambient temperature, poured into water, and extracted with EtOAc. The organic layer was washed with brine, dried, and concentrated. The residue was purified by chromatography on silica gel using n-hexane/EtOAc, 70 30 to 60 40. The two products, N-t-butoxycarbony l-spiro[(2-hydroxy )indane-1,4Cpiperidine] and N-t-butoxycarbonyl-spiro[(3-hydroxy)indane-1,4 -piperidine] were isolated in 55% and 40% yields, respectively. H-NMR, IR, and MS data supplied. 

To a solution of the product from Step 3 (9.08 mmol) dissolved in 30 ml N,N-dimethylformamide was added 4-(2-chloroethyl)morpholine hydrochloride (27.2 mmol) and K2CO3 (27.2 mmol). Thereafter, the solution was heated to 63 °C 24 hours. Additional K2CO3 (9.08 mmol) and 4-(2-chloroethyl)-morpholine hydrochloride (9.08 mmol) were added and the mixture re-heated for an additional 24 hours at 63 °C. The mixture was partitioned between EtOAc and water, the organic phase washed 3 times with 30 ml brine, dried, and concentrated. The residue was purified by flash chromatography using EtOAc/hexane, 2 8, and 5.21 g product isolated. MS and elemental analysis data supplied. 

The product from Step 5 (11 mmol) was dissolved in 10 ml N,N-dimethylformamide, the product from Step 2 (7.7 mmol) and K2CO3 (8.8 mmol) added, and the mixture stirred at ambient temperature for 16 hours. The solvent was removed and the residue partitioned between EtOAc and water. The organic phase was separated, washed, dried, concentrated, purified by flash chromatography on silica gel using 0-4% methyl alcohol/CH2Cl2, and the product isolated as a yellow solid. MS data supplied. 

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