Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][CH:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:4][CH2:3]1.C(N(CC)C(C)C)(C)C.[CH3:22][O:23][CH2:24]Cl.Cl>ClCCCl.O>[CH3:22][O:23][CH2:24][O:1][CH:2]1[CH2:3][CH2:4][CH:5]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:7]1
Reactant: COCCl
Reactant: CCOC(=O)C1CCC(O)CC1
Agent: Cl
Solvent: O
Solvent: ClCCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)C1CCC(OCOC)CC1
Temperature: 25 °C
Yield: 41.5 %

Procedure:
To a stirred solution of ethyl 4-oxocyclohexanecarboxylate (2.0 g, 12 mmol) in 10 mL of ethanol at 5° C. was added, in portions, 0.5 g (13 mmol) of sodium borohydride. After the mixture was stirred for 30 minutes at 5° C. and 18 hours at room temperature it was diluted with 10 mL of water and acidified to pH 3 with 1N hydrochloric acid. The mixture was extracted with ethyl acetate. After being washed with water and brine the extracts were dried over anhydrous sodium sulfate and concentrated to give ethyl 4-hydroxycyclohexanecarboxylate as a colorless liquid. This alcohol (2.08 g, 25 mmol) in 12 mL of 1,2-dichloroethane at room temperature was added to 4.10 mL (23.1 mmol) of N,N-diisopropylethylamine and 1.65 mL (21.7 mmol) of chloromethyl methyl ether. The resulting mixture was stirred and refluxed for 24 hours, cooled to room temperature, diluted with 20 mL of water, acidified to pH 3 with hydrochloric acid and extracted with methylene chloride (3×20 mL). The combined organic layers were washed with 1N hydrochloric acid, dried over anhydrous sulfate, and concentrated. The resulting liquid was purified by flash chromatography (silica gel, 17% ether in low boiling petroleum ether) to give 1.95 g (79.2%) of ethyl 4-methoxymethyloxycyclohexanecarboxylate. This ester (1.91 g, 8.83 mmol) was hydrolyzed by stirring with lithium hydroxide hydrate (0.75 g, 18 mmol) in a solution of methanol (20 mL) and water (5 mL) at room temperature for 24 hours. The mixture was diluted with 20 mL of water and extracted with ether. The aqueous part was acidified to the Congo Red endpoint, salted with sodium chloride, and extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate, and concentrated to give the 4-methoxymethyloxycylohexanecarboxylic acid (1.47 g, 88.6%) as a colorless liquid, IR (neat) 3500-2400 (broad), 1704 cm-1. To a stirred solution of this acid (1 4 g, 7.44 mmol), 0.03 mL (0.4 mmol) of dimethylformamide, and 0.6 mL (7.5 mmol) of pyridine in 20 mL of methylene chloride at 5° C. under argon was added 0.67 mL (7.5 mmol) of oxalyl chloride. After the mixture was stirred for 5 minutes at 5° C. and 30 minutes at room temperature, it was added to a solution of 5,6-diamino-1,3-di-n-propyluracil (1.68 g, 7.42 mmol) and pyridine (0.7 mL, 8.7 mmol) in 15 mL of methylene chloride. After 15 minutes at 5° C. and 1 hour at room temperature the resulting solution was diluted with water (25 mL), acidified to pH 1 with 5N hydrochloric acid, and the layers were separated. The aqueous layer was extracted with methylene chloride (3×25 mL), the combined organic extracts were washed with a saturated aqueous solution of sodium bicarbonate, and dried over sodium sulfate. Concentration gave the intermediate amide as a yellow amorphous semi-solid. A stirred solution of the crude amide, hexamethyldisilazane (HMDS) (8.0 mL, 37.1 mmol), and ammonium sulfate (0.1 g, 0.76 mmol) in 20 mL of dioxane was refluxed for 19 hours. The mixture was cooled to room temperature, treated with 5 mL of methanol and stirred for 1 hour. The suspension was concentrated to dryness, the resulting solid was triturated with 25 mL of ether, filtered, washed twice with 10 mL portions of ether, twice with 10 mL portions of low boiling petroleum ether and dried in vacuo at room temperature to give a mixture (2.15 g, 76.8%) of trans and cis-1,3-di-n-propyl-8-(4-methoxymethyloxycyclohexyl)xanthine. The xanthine (1.63 g, 4.31 mmol), together with concentrated hydrochloric acid (10 drops), in 25 mL of methanol was stirred and refluxed for 18 hours. Upon cooling to room temperature, solids that precipitated from the mixture were filtered, washed with three 5 mL portions of ether and dried in vacuo at 110° C. over phosphorous pentoxide for 18 hours to give 1.03 g (75.1%) of a white solid: mp 223-225° C.; IR (KBr) cm-1 3417, 3149, 1700, 1653, 1553, 1499, 1393; 1H NMR (300 MHz, DMSO) 0.85 (m, 6H), 1.10-2.10 (m, 12H), 2.70 (m, 1H), 3.40 (m, 1H), 3.85 (m, 4H), 4.39 & 4.62 (2×d, 1H total), 13.10 (2×s, 1H total). Anal. calcd for C17H26N4O3 : C, 61.06; H, 7.84; N, 16.75. Found: C. 61.04; H, 7.84; N, 16.72.