Reaction SMILES: [C:1]1([CH:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12](C)[CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.Cl[C:24]([O:26][CH2:27][CH3:28])=[O:25]>C1(C)C=CC=CC=1>[C:16]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:11][CH2:10]2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: CN1CCC(OC(c2ccccc2)c2ccccc2)CC1
Reactant: CCOC(=O)Cl
Agent: Cl
Solvent: Cc1ccccc1
Product: CCOC(=O)N1CCC(OC(c2ccccc2)c2ccccc2)CC1
Temperature: 104 °C
Yield: 72 %

Procedure:
4-(Diphenylmethoxy)-1-(methyl)piperidine (prepared by neutralization of the commercial HCl salt; 4 g, 14.2 mmol, 1 equiv.) in anhydrous toluene (20 mL) was stirred at room temperature under nitrogen. Ethyl chloroformate (4.66 g, 43 mmol, 4.1 mL, 3 equiv.) was added dropwise over 5 minutes, whereupon significant effervescence was noted. The mixture was heated over the course of 1 h to reflux with an oil bath (bath temperature 104° C.). The mixture was then cooled to room temperature, whereupon more ethyl chloroformate (4 mL) was added. The mixture was heated at reflux (bath T=104° C.) for 7 h and again cooled to room temperature. The cooled mixture was concentrated and the residue purified by dry column chromatography (4×8.5 cm silica bed; 2:1 heptane:ethyl acetate) to yield 3.49 g (72%) of 4a as a slightly yellow oil. 1H NMR was consistent with the structure. 4-(diphenylmethoxy)piperidine (5). 4-(Diphenylmethoxy)-1-(ethoxycarbonyl)piperidine (4a) (11.45 g, 33.7 mmol) was dissolved in ethanol (72 mL). A cold solution of sodium hydroxide (8.2 g, 205 mmol) in water (12 mL) was added slowly and a small amount of heat was detected. The mixture was heated at reflux for 17 h and then cooled to room temperature. The mixture was subsequently diluted with water (100 mL) and ethyl acetate (100 mL) and stirred for 0.5 h to dissolve the resultant solid. The organic and aqueous layers were separated and the organic layer was washed with water (100 mL). The separate aqueous layers were extracted with ethyl acetate (100 mL) and the organic layers were combined, dried with Na2SO4, filtered and concentrated to yield 7.88 g (87.5%) of 5 as a viscous yellow oil. The structure was confirmed by 1H NMR. Methyl 3-[4-(diphenylmethoxy)piperidin-1-yl]propanoate (6b). A solution of 4-(diphenylmethoxy)piperidine (5) (1.4 g, 5.2 mmol), methyl acrylate (560 mg, 6.5 mmol) and methanol (9.5 mL) was placed on a preheated orbital shaker at 75° C. for 3 h. The yellow solution was concentrated to yield 1.8 g (98%) of 6b as a yellow oil. The structure was confirmed by 1H NMR. (The propanoate esters 6c and 6e were similarly prepared.) Isopropyl 3-[4-(diphenylmethoxy)piperidin-1-yl]propanoate (6d). Oxalyl chloride (7.27 g, 57.3 mmol, 5 mL) was added in one aliquot, with stirring, to a pre-cooled (ice bath) solution of 6a-HCl (1.14 g, 3.0 mmol) in dry THF. Once the initial effervescence ceased, the flask was sealed under nitrogen and the mixture was stirred for 1.75 h. The magnetic stirring bar was washed with dry THF upon its removal from the solution mixture and the mixture was then concentrated on a rotary evaporator to give a yellow-white solid. The solid was dried under high vacuum for 1 h. The solid was then suspended in 2-propanol (15 mL) and 4-ethylmorpholine (440 mg, 400 μL, 3.8 mmol, 1.28 equiv.) was added. Vapors formed above the suspension and the slurry became an orange-yellow solution after about 2 minutes. After having been stirred for 2.5 days, the reaction mixture was concentrated. The residue was dissolved in dichloromethane (25 mL) and washed with 1 N KOH (15 mL). The layers were separated and the aqueous layer was extracted with dichloromethane (25 mL). Both organic layers were washed with water (25 mL), combined, dried with Na2SO4, filtered and concentrated to yield 976 mg (84%) of a dark orange-yellow oil. This oil was purified by flash chromatography (2:1 heptane:ethyl acetate) to yield 774 mg (67%) of 6d as a yellow oil. 1H NMR and LC/MS confirmed the structure. (The propanoate ester 6f was similarly prepared.) Isopropyl 3-[4-(diphenylmethoxy)piperidin-1-yl]propanoate (6d), Alternate procedure. Sodium hydride (60% dispersion in mineral oil, about 15 mg) was added to a stirred solution of 6b (384 mg, 1.09 mmol) in 2-propanol (8 mL). Although after only 1 h there was no insoluble solid, TLC showed evidence of degradation to the acid 6a. After confirmation by TLC that the reaction was complete, the mixture was concentrated and dissolved in a small amount of 2:1 heptane:ethyl acetate for flash chromatography. The insoluble solid was isolated by filtration (58 mg) and was shown to be 6a. The solution was purified by flash chromatography to yield 300 mg (72%) of 6d as a colorless oil. Purity (LC/MS): 99.6% (m/z=381). (The propanoate ester 6f was also prepared by this alternate procedure.) 3-[4-(diphenylmethoxy)piperidin-1-yl]propanoic acid hydrochloride (6a-HCl). A solution of sodium hydroxide (1.3 g, 32.5 mmol, 1.98 equiv.) in water (16 mL) was slowly added to a stirring solution of 6b (5.8 g, 16.4 mmol) in methanol (58 mL) at room temperature, resulting in a slight increase in temperature. The solution was heated at reflux for 1.25 h, cooled to room temperature, and concentrated. The resulting residue was dissolved in water (75 mL) and the pH was adjusted to 2 with concentrated HCl (about 2.5 mL). The thick mixture was then extracted with chloroform (3×80 mL; 6a-HCl is soluble in chloroform) and the combined organic layers were washed with brine (100 mL). The organic layers were dried with Na2SO4, filtered, and concentrated to give 6a-HCl as white needles (5.3 g, 86%). The structure was confirmed by 1H NMR and LC/MS. Ethyl 3-[4-(diphenylmethoxy)piperidin-1-yl]propanoate, oxalic acid salt (6c-Ox). A solution of oxalic acid (130 mg, 1.44 mmol) in ethanol (3 mL) was added in one aliquot to a stirred solution of ethyl 3-[4-(diphenylmethoxy)piperidin-1-yl]propanoate 6c (530 mg, 1.44 mmol) in ethanol (3 mL). The mixture became solid at the end of the addition, whereupon more ethanol (2 mL) was added to facilitate stirring. After 1 h of stirring, the solid was collected by suction filtration and washed with ethanol (2 mL). After drying, the oxalate salt 6c-Ox was obtained as white powder (595 mg, 90%). 1H NMR, LC/MS, and elemental analysis were consistent with the structure. (The oxalate salts of 6d, 16e, and 6f were similarly prepared.)