Reaction SMILES: [CH3:1][NH:2][C:3](=[O:5])[CH3:4].[H-].[Na+].[CH3:8][C:9]1([O:12][CH2:13][CH2:14]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:11][CH2:10]1>O1CCCC1>[CH3:1][N:2]([CH2:14][CH2:13][O:12][C:9]1([CH3:8])[CH2:11][CH2:10]1)[C:3](=[O:5])[CH3:4]
Reactant: Cc1ccc(S(=O)(=O)OCCOC2(C)CC2)cc1
Reactant: CNC(C)=O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(=O)N(C)CCOC1(C)CC1
Temperature: 25 °C
Reaction time: 22 h
Yield: 20.1 %

Procedure:
Dissolve 2-(1-methylcyclopropoxy)ethanol (362.3 mg, 3.12 mmol) (see Tet. Lett. 1999, 40, 8647-8650) and triethylamine (473.4 mg, 4.68 mmol) in 10 mL methylene chloride at 0° C. Dissolve para-toluenesulfonyl chloride (596.1 mg, 3.12 mmol) in 10 mL methylene chloride and add it dropwise to the reaction. After 30 minutes raise the reaction to room temperature and allow it to stir for 24 hours. Dilute the reaction with methylene chloride and wash it with water (1×), 1N HCl (1×), saturated aqueous sodium hydrogen carbonate (1×) and brine (1×). Dry the organic layer with magnesium sulfate. Filter and remove the solvent in vacuo to give 670.1 mg of crude toluene-4-sulfonic acid 2-(1-methylcyclopropoxy)ethyl ester. Dissolve N-methylacetamide (176.9 mg, 2.42 mmol) in 5 mL tetrahydrofuran and add it dropwise to a slurry of sodium hydride (122.9 mg, 3.07 mmol) in 5 mL tetrahydrofuran. Allow the reaction to stir at room temperature for 22 hours. Dissolve the crude toluene-4-sulfonic acid 2-(1-methylcyclopropoxy)ethyl ester (670.1 mg, 2.48 mmol) in 5 mL tetrahydrofuran and add it dropwise to the reaction mixture. After the addition is complete, heat the reaction to reflux and allow it to stir for 26 hours. Cool the reaction and remove the solvent in vacuo. Dissolve the residue in methylene chloride and wash with brine (1×). Dry the organic layer with magnesium sulfate. Filter and remove the solvent in vacuo to afford 276.9 mg of crude material. Purify the residue by Biotage chromatography (50% EtOAc/Hexanes to 30% MeOH/EtOAc) to afford 83.3 mg of N-methyl-N-(2-(1-methylcyclopropoxy)ethyl)acetamide. Dissolve this material (83.3 mg, 0.486 mmol) in 10 mL of toluene and add Lawesson's reagent (102.5 mg, 0.253 mmol) to the mixture. Heat the reaction to 75° C. and allow it to stir for 24 hours. Remove the solvent in vacuo. Triturate the residue with diethyl ether three times decanting carefully from the residual solids. Combine the decanted layers and remove the solvent in vacuo to afford 47.0 mg of crude N-methyl-N-(2-(1-methylcyclopropoxy)ethyl)thioacetamide. Dissolve this crude material (47.0 mg, 0.251 mmol) in 10 mL diethyl ether, add MeI (excess) and allow the reaction to stir for 21 hours. Decant the diethyl ether from the oil and triturate the oil with diethyl ether (2×). Remove any excess diethyl ether from the oily residue in vacuo to obtain 46.5 mg of crude HI salt of methyl-(2-(1-methylcyclopropoxy)ethyl)-(1-methylsulfanylethyl)amine as an oil. Dissolve this crude material (46.5 mg, 0.141 mmol) in 10 mL of pyridine and add 3,2′-difluorobiphenyl-4-carboxylic acid (R)-(6-amino-2(R)-hydroxyindan-1-yl)amide (49.6 mg, 0.130 mmol) and allow the reaction to stir at room temperature for 20 hours. Remove the solvent in vacuo and dissolve the residue in methylene chloride and wash with saturated aqueous sodium hydrogen carbonate. Dry the organic layer with magnesium sulfate. Filter and remove the solvent in vacuo to give 39.2 mg of crude product. Purify via silica gel column chromatography (2% MeOH/CHCl3) to afford 10.7 mg of the titled product (15% yield). MS (ES): m/z 534.2 (M+H).