Reaction SMILES: O.[Na].[CH3:3][C:4]([SH:7])([CH3:6])[CH3:5].[H-].[Na+]>CC(C)=O.Cl.C(Cl)Cl.C1COCC1.CO.C(Cl)Cl>[C:4]([S:7][C:4]([CH3:6])([CH3:5])[CH3:3])([CH3:6])([CH3:5])[CH3:3]
Reactant: CC(C)(C)S
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)SC(C)(C)C
Temperature: 0 °C
Reaction time: 18 h
Yield: 271.3 %

Procedure:
2-Methoxy methyl phenylacetate was prepared by refluxing 2-methoxy phenylacetate (10.2 g, 61.3 mmole), 70 mL of anhydrous methanol and 1.5 mL of concentrated sulfuric acid for 17 hours. The solvent was removed and the oil was dissolved in 100 mL of diethyl ether, washed with saturated NaHCO3, dried, filtered and evaporated to give 9.26 grams (83%) of 2-methoxymethyl phenylacetate. This material (10.0 g, 55.0 mmole) dissolved in 6 mL of tetrachloroethane was added over a period of 25 minutes (making sure that the temperature of the reaction mixture did not exceed 50° C.) to AlCl3 (15 g, 112 mmole) in 50 mL of tetrachloroethane to which was added 2-bromopropionyl chloride (5.7 mL, 56.5 mmole) and the mixture heated at 45° C. for 20 minutes. The reaction was allowed to stir at 50° C. for 5 hours then at room temperature for 10 hours, poured onto 150 mL ice and 0.5 mL of concentrated HCl was added. The mixture was extracted with CH2Cl2 and the organic layer washed with 10% NaOH, and H2O, dried, filtered and evaporated to give a dark purple-red oil which was purified by flash chromatography (SiO2, first with 50% hexane-CH2Cl2 then with CH2Cl2) to afford 11.6 grams (66% yield) of methyl [3-(2-bromopropionyl)-6-methoxyphenyl]acetate as a thick oil: Rf =0.44 (SiO2, CH2Cl2). This material (11.4 g, 36.3 mmole) was dissolved in 70 mL of acetone and 15 mL of concentrated HCl, 20 mL of H2O were added and the resulting solution refluxed for 6 hours. The volatiles were removed to give an oil/water mixture which was then dissolved in 100 mL of CH2Cl2. The mixture was extracted with 150 mL of saturated NaHCO3. The aqueous was then removed and acidified with concentrated HCl to a pH=1. The aqueous mixture was then quickly extracted with 100 mL of CH2Cl2. The organic layer was then dried, filtered, and evaporated to give 6.0 g (64%) of as a white solid: Rf =0.6 (SiO2, 10% methanol-CH2Cl2). To the sodium salt of 2-methyl-2-propanethiol (0.9 g, 8.82 mmole) was added sodium hydride (0.25 g, 11.3 mmole) and 15 mL of anhydrous tetrahydrofuran and mixture cooled to 0° C. To the mixture was added the above 3-[(2-chloropropionyl)-6-methoxyphenyl]acetate (1.5 g, 5.84 mmole) dissolved in 15 mL of anhydrous THF over a period of 10 minutes. After addition, the reaction mixture was stirred, at room temperature under nitrogen for 18 hours, the volatile components removed and dissolved in 80 mL of H2O and the aqueous washed with 100 mL of diethyl ether. The aqueous layer was then acidified with 1 mL of concentrated HCl (pH=1) and extracted with ether. The organic layers were combined, dried, filtered, and evaporated to give 1.75 grams of the t-butyl thioether product which was used without any further purification. To 1.75 g (5.64 mmole) of this material was added 2 mL of DMF, 4 mL of concentrated acetic acid, and 1 mL of H2O. To the solution was then added 2-nitrobenzenesulfenyl chloride (1.6 g, 8.44 mmole) then stirred for 24 hours. The volatile components were removed under reduced pressure to give an oil/water mixture. To the mixture was then added 15 mL of H2O, cooled to freezing, and then lyophilized overnight. After lyophilization, the remaining solid was taken up in CH2Cl2 and purified by flash chromatography (SiO2, first with CH2Cl2, then with 50% diethyl ether-CH2Cl2 and then with 10% methanol-CH2Cl2) to isolate a yellow oil which crystallized upon standing to give 1.41 grams (59%) of a yellow crystalline solid: Rf =0.37 (SiO2, 10% methanol-CH2Cl2). Coupling of this material to TentaGel® resin was accomplished by placing TentaGel® (3.0 g, 0.87 mmole of amine), 50 mL CH2Cl2 and 1 mL DIEA (6.46 mmole) in a peptide synthesis vessel and the mixture shaken for 5 minutes followed by washing with CH2Cl2. To this was added 20 mL CH2Cl2 followed by 3-[2-[(2-nitrophenyl)dithio]propionyl]-6-methoxyphenylacetic acid from above (0.9 g, 2.2 mmole) dissolved in 30 mL of CH2Cl2 and mixture shaken for 30 seconds. To the mixture was added (0.3 mL, 2.1 mmole) diisopropylcabodiimide (DIC) and mixture shaken for 7 hours, filtered, washed with CH2Cl2, methanol, and CH2Cl2. The resin was then placed under pump vacuum for several hours to give 3.2 grams of the final resin material as a yellow solid. The amount of disulfide on the resin was determined by a modified Ellman spectrophotometric assay at 490 nm (0.18 mmole of disulfide/g of resin). To the resin (2.3 g, 0.43 mmole) was added 150 mL DMF, β-mercaptoethanol (0.25 mL, 3.5 mmole) and diisopropylethylamine (0.4 mL, 2.3 mmole) and the mixture shaken for 2-3 minutes, filtered, and the process repeated two more times using the same quantities of BME and DIEA. The resin was then washed five times with DMF, three times with methanol, four times with CH2Cl2 and then three times with DMF to afford 19.