2-(3,4-dimethoxyphenyl)acetonitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In carrying out this synthesis, the following materials were used. Homovanillyl alcohol, Aldrich, 99%, Cat. No. 148830-10G, Batch No. 19516EO; potassium carbonate, Aldrich, 99%; triethylamine, Aldrich, 99.5%, Cat. No. 471283-500 mL, Batch No. 04623HD; methanesulfonyl chloride, Aldrich, 99.5%, Cat. No. 471259-500 mL, Batch No. 13209KC; 3.4-dimethoxyphenylacetonitrile, Aldrich, Cat. No. 126349-100G, Batch No. 08011BD; 2-iodopropane, Aldrich, 99%, Cat. No. 148938-100G, Batch #, 03604DD; diisopropylamine, redistilled, Aldrich, 99.95%, Cat. No. 386464-100 mL, Batch #00944TD; butyllithium, 1.6 M solution in hexanes, Aldrich, Cat. No. 186171-100 mL, Batch #20709PD; 3-bromo-1-propanol, Aldrich, 97%, Cat. No. 167169-25G, Batch No. 0901DE; dichloromethane, Aldrich, Cat. No. 270997-2L, Batch #: 004341CD; sodium triacetoxyborohydride, Aldrich, 95%, Cat. No. 316393-25G, Batch No. 07920LD; N,N-diisopropylethylamine, Aldrich, Cat. No. 387649-100 mL, Batch No. 06448PC; N-methylhomoveratrylamine, Aldrich, Cat. No. 334774, Batch No. 10421EO. this synthesis diisopropylamine, redistilled

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of butyllithium (1.6 M solution in hexanes, 7.0 mL, 11.2 mmol) was added via syringe to a solution of diisopropylamine (1.5 mL, 10.61 mmol) in anhydrous THF (25 mL) at −78° C. And then a solution of 2-(3,4-dimethoxyphenyl)-4-(1,3)-dioxolan-2-yl-butyronitrile (18) (709 mg, 2.56 mmol) (previously prepared by reacting 2-(2-bromoethyl)-1,3-dioxolane with 2-(3,4-dimethoxyphenyl)-acetonitrile (14) in a solution diisopropylamine to which butyllithium was added) in THF (10 mL) was added via syringe. The mixture was stirred at −78° C. for five minutes and then 2-iodopropane (0.4 mL, 3.96 mmol) was added. The mixture was stirred at −78° C. for five hours and then at room temperature for 17.5 hours., Saturated NH4Cl solution (10 mL) was added to quench the reaction. Ethyl ether (60 mL) was added and the etheral solution was isolated. The aqueous solution was extracted with ether (2×20 mL). After washing with brine, drying with sodium sulfate, the solvent was removed under reduced pressure and the residue was purified by flash column chromatography on SiO2 using EtOAc/hexanes (0-30%) to afford the product (19) (397 mg) in 49% yield. 1H-NMR (CDCl3): δ 6.86-6.82 (m, 3 H), 4.80 (t, J=4.2-4.8 Hz, 1 H), 3.95-3.77 (m, 4 H), 3.878 (s, 3 H), 3.867 (s, 3 H), 2.24 (dt, J=3.9-4.2 Hz, J=12.9-13.2 Hz, 1 H), 2.11-2.02 (m, 1 H), 1.91 (dt, J=3.9 Hz, J=12.6 Hz, 1 H), 1.72 (tt, J=3.9-4.2 Hz, J=12.6-13.2 Hz, 1 H), 1.37-1.24 (m, 1 H), 1.16 (d, J=6.6 Hz, 3 H), 0.80 (d, J=6.9 Hz, 3 H). LC-MS: 342.083 (MNa+). was added via syringe The mixture was stirred at −78° C. for five hours at room temperature for 17.5 hours to quench the reaction the etheral solution was isolated The aqueous solution was extracted with ether (2×20 mL) After washing with brine drying with sodium sulfate the solvent was removed under reduced pressure the residue was purified by flash column chromatography on SiO2