1-(iodomethyl)-4-methoxybenzene

Conditions: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 880 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF are added dropwise, at -70° C., under an argon atmosphere and within the space of 20 min, to 130 g (400 mmol) of 5(S)-[1(S)-(Boc-amino)-2-cyclohexylethyl]dihydrofuran-2-(3H)-one which is dissolved in 1000 ml of abs. THF and 108 ml of DMPU. After 20 min, a solution of 110 g (443 mmol) of p-methoxybenzyl iodide [preparation, see Example 7e)] in 60 ml of abs. THF is added dropwise, and this mixture is thoroughly stirred at -75° C. for 2 h. The mixture is subsequently protonated at -70° C. with 152 ml of propionic acid followed by 250 ml of water (temperature rises to -20° C.); 1 l of ethyl acetate is then added and the reaction mixture is poured onto 2 l of 15% NaHCO3 solution. The aqueous phase is separated off and extracted with 1 l of ethyl acetate. The organic phases are washed 2× with sat. NaHCO3 solution, water and saline, dried with Na2SO4 and evaporated. Column chromatography (SiO2, hexane/ethyl acetate, 9:1) and crystallization from hexane yields the pure title compound: TLC Rf (E)=0.45; tRet (II)=8.6 min; FAB-MS (M+H)+ =432. is dissolved in 1000 ml of abs The aqueous phase is separated off extracted with 1 l of ethyl acetate The organic phases are washed 2× with sat. NaHCO3 solution, water and saline dried with Na2SO4 evaporated Column chromatography (SiO2, hexane/ethyl acetate, 9:1) and crystallization from hexane

Conditions: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 880 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF are added dropwise, at -70° C., under an argon atmosphere and within the space of 20 min, to 130 g (400 mmol) of 5(S)-[1(S)-(Boc-amino)-2-cyclohexylethyl]dihydrofuran-2-(3H)-one which is dissolved in 1000 ml of abs. THF and 108 ml of DMPU. After 20 min, a solution of 110 g (443 mmol) of p-methoxybenzyl iodide [preparation, see Example 7e)] in 60 ml of abs. THF is added dropwise, and this mixture is thoroughly stirred at -75° C. for 2 h. The mixture is subsequently protonated at -70° C. with 152 ml of propionic acid followed by 250 ml of water (temperature rises to -20° C.); 1 l of ethyl acetate is then added and the reaction mixture is poured onto 2 l of 15% NaHCO3 solution. The aqueous phase is separated off and extracted with 1 l of ethyl acetate. The organic phases are washed 2× with sat. NaHCO3 solution, water and saline, dried with Na2SO4 and evaporated. Column chromatography (SiO2, hexane/ethyl acetate, 9:1) and crystallization from hexane yields the pure title compound: TLC Rf (E)=0.45; tRet (II)=8.6 min; FAB-MS (M+H)+ =432. is dissolved in 1000 ml of abs The aqueous phase is separated off extracted with 1 l of ethyl acetate The organic phases are washed 2× with sat. NaHCO3 solution, water and saline dried with Na2SO4 evaporated Column chromatography (SiO2, hexane/ethyl acetate, 9:1) and crystallization from hexane

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

Procedure: In analogy with Example 5d), 2.9 g (7.04 mmol) of 5(S)-[1(S)-(Boc-amino)-2-(p-benzyloxy-phenyl)ethyl]dihydrofuran-2-(3H)-one [preparation, see Example 1g)], dissolved in 10.3 ml of THF and 1.2 ml of DMPU, are deprotonated, at -70° C., with 14.1 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF, and alkylated (at from -75° C. to -50° C.), with 2.6 g (10.57 mmol) of p-methoxybenzyl iodide [preparation, see Example 7e)] in 10 ml of THF. Protonation, at -75° C., with 2.6 ml (35.2 mmol) of propionic acid and 2.6 ml of water, extraction and column chromatography (SiO2, hexane/ethyl acetate, 2:1) affords the title compound: TLC Rf (D)=0.48; tRet (II)=18.8 min. (at from -75° C. to -50° C.)

Conditions: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 880 ml of a 1 M solution of lithium bis(trimethylsilyl)amide in THF are added dropwise, at -70° C., under an argon atmosphere and within the space of 20 min, to 130 g (400 mmol) of 5(S)-[1(S)-(Boc-amino)-2-cyclohexylethyl]dihydrofuran-2-(3H)-one which is dissolved in 1000 ml of abs. THF and 108 ml of DMPU. After 20 min, a solution of 110 g (443 mmol) of p-methoxybenzyl iodide [preparation, see Example 7e)] in 60 ml of abs. THF is added dropwise, and this mixture is thoroughly stirred at -75° C. for 2 h. The mixture is subsequently protonated at -70° C. with 152 ml of propionic acid followed by 250 ml of water (temperature rises to -20° C.); 11 of ethyl acetate is then added and the reaction mixture is poured onto 2 l of 15% NaHCO3 solution. The aqueous phase is separated off and extracted with 1 l of ethyl acetate. The organic phases are washed 2× with sat. NaHCO3 solution, water and saline, dried with Na2SO4 and evaporated. Column chromatography (SiO2, hexane/ethyl acetate, 9:1) and crystallization from hexane yields the pure title compound: TLC Rf (E)=0.45; tRet (II)=18.6 min; FAB-MS (M+H)+ =432. is dissolved in 1000 ml of abs The aqueous phase is separated off extracted with 1 l of ethyl acetate The organic phases are washed 2× with sat. NaHCO3 solution, water and saline dried with Na2SO4 evaporated Column chromatography (SiO2, hexane/ethyl acetate, 9:1) and crystallization from hexane

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

Procedure: A solution of 1.7 ml (12.8 mmol) of 4-methoxybenzyl chloride (Fluka; Buchs/Switzerland) in 25 ml of acetone is stirred, at RT, together with 9.4 g (62.6 mmol) of sodium iodide. A gas chromatogram of the reaction mixture, carried out after 90 min, indicates that the reaction is complete; the reaction mixture is therefore poured onto ether and this mixture is washed with 10% sodium thiosulfate solution and saline. Drying the organic phase with Na2SO4, and evaporating it, affords the title compound: 1H-NMR (200 MHz, CD3OD: 3.78 (s, 3H), 4.54 (s, 2H), 6.8-6.95 and 7.2-7.4 (2m, each 2H). the reaction mixture is therefore poured onto ether this mixture is washed with 10% sodium thiosulfate solution and saline Drying the organic phase with Na2SO4 evaporating it

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

Procedure: In analogy with Example 5d), 2.9 g (7.04 mmol) of 5(S)-[1(S)-(Boc-amino)-2-(p-benzyloxy-phenyl)ethyl]dihydrofuran-2-(3H)-one (preparation, see Example 1g)], dissolved in 10.3 ml of THF and 1.2 ml of DMPU, are deprotonated, at -70° C., with 14.1 ml of a 1 M solution of lithium bis(trimethylsilyl)amide in THF, and alkylated (at from -75° C. to -50° C.), with 2.6 g (10.57 mmol) of p-methoxybenzyl iodide [preparation, see Example 7e)] in 10 ml of THF. Protonation, at -75° C., with 2.6 ml (35.2 mmol) of propionic acid and 2.6 ml of water, extraction and column chromatography (SiO2, hexane/ethyl acetate, 2:1) affords the title compound: TLC Rf (D)=0.48; tRet (II)=18.8 min. (at from -75° C. to -50° C.)

Conditions: temp:-75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 880 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF are added dropwise, at -70° C., under an argon atmosphere and within the space of 20 min, to 130 g (400 mmol) of 5(S)-[1(S)-(Boc-amino)-2-cyclohexylethyl]dihydrofuran-2-(3H)-one which is dissolved in 1000 ml of abs. THF and 108 ml of DMPU. After 20 min, a solution of 110 g (443 mmol) of p-methoxybenzyl iodide [preparation, see Example 7e)] in 60 ml of abs. THF is added dropwise, and this mixture is thoroughly stirred at -75° C. for 2 h. The mixture is subsequently protonate at -70° C. with 152 ml of propionic acid followed by 250 ml of water (temperature rises to -20° C.); 1 l of ethyl acetate is then added and the reaction mixture is poured onto 2 l of 15% NaHCO3 solution. The aqueous phase is separated off and extracted with 1 l of ethyl acetate. The organic phases are washed 2× with sat. NaHCO3 solution, water and saline, dried with Na2SO4 and evaporated. Column chromatography (SiO2, hexane/ethyl acetate, 9:1) and crystallization from hexane yields the pure title compound: TLC Rf (E)=0.45; tRet (II)=18.6 min; FAB-MS (M+H)+ =432. is dissolved in 1000 ml of abs The aqueous phase is separated off extracted with 1 l of ethyl acetate The organic phases are washed 2× with sat. NaHCO3 solution, water and saline dried with Na2SO4 evaporated Column chromatography (SiO2, hexane/ethyl acetate, 9:1) and crystallization from hexane

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

Procedure: A solution of 1.7 ml (12.8 mmol) of 4-methoxybenzyl chloride (Fluka; Buchs/Switzerland) in 25 ml of acetone is stirred, at RT, together with 9.4 g (62.6 mmol) of sodium iodide. A gas chromatogram of the reaction mixture, carried out after 90 min, indicates that the reaction is complete; the reaction mixture is therefore poured onto ether and this mixture is washed with 10% sodium thiosulfate solution and saline. Drying the organic phase with Na2SO4, and evaporating it, affords the title compound: 1H-NMR (200 MHz, CD3OD: 3.78 (s, 3H), 4.54 (s, 2H), 6.8-6.95 and 7.2-7.4 (2m, each 2H). the reaction mixture is therefore poured onto ether this mixture is washed with 10% sodium thiosulfate solution and saline Drying the organic phase with Na2SO4 evaporating it

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

Procedure: In analogy with Example 5d), 2.9 g (7.04 mmol) of 5(S)-[1(S)-(Boc-amino)-2-(p-benzyloxy-phenyl)ethyl]dihydrofuran-2-(3H)-one [preparation, see Example 1g)], dissolved in 10.3 ml of THF and 1.2 ml of DMPU, are deprotonated, at -70° C., with 14.1 ml of a 1M solution of lithium bis(trimethylsilyl)amide in THF, and alkylated (at from -75° C. to -50° C.), with 2.6 g (10.57 mmol) of p-methoxybenzyl iodide [preparation, see Example 7e)] in 10 ml of THF. Protonation, at -75° C., with 2.6 ml (35.2 mmol) of propionic acid and 2.6 ml of water, extraction and column chromatography (SiO2, hexane/ethyl acetate, 2:1) affords the title compound: TLC Rf (D)=0.48; tRet (II)=18.8 min. (at from -75° C. to -50° C.)

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

Procedure: 2.98 g (9.74 mmol) of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-dihydrofuran-2-(3H)-one dissolved in 40 ml of THF are deprotonated at -75° C. with 19.5 ml of lithium bis(trimethylsilyl)amide 1M in THF and alkylated with 2.9 g (11.7 mmol) of p-methoxybenzyl iodide in 20 ml of THF (45 min). Column chromatography (SiO2, hexane/ethyl acetate 2:1) and digestion using diisopropyl ether yield the pure title compound; TLC Rf (D)=0.32; tRet (I)=16.7 min.

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

Procedure: A solution of 1.7 ml (12.8 mmol) of 4-methoxybenzyl chloride (Fluka; Buchs/Switzerland) in 25 ml of acetone is stirred with 9.4 g (62.6 mmol) of sodium iodide at room temperature. Gas chromatography of the reaction mixture after 90 minutes indicates that the reaction is complete, and the reaction mixture is therefore poured onto ether and washed with 10% sodium thiosulfate solution and brine. Drying of the organic phase with Na2SO4 and concentration by evaporation yield the title compound; 1H-NMR (200 MHz, CD3OD: 3.78 (s, 3 H), 4.54 (s, 2 H), 6.8-6.95 and 7.2-7.4 (2m, each 2 H). the reaction mixture is therefore poured onto ether washed with 10% sodium thiosulfate solution and brine Drying of the organic phase with Na2SO4 and concentration by evaporation