(4-methoxyphenyl)methyl 2,2,2-trichloroethanimidate

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: To a solution of compound 30 (3.50 g, 12.9 mmol) and 4-methoxybenzyl trichloroacetimidate (4.65 g, 17.3 mmol) in DCM (100 mL) was added camphorsulfonic acid (450 mg, 1.92 mmol). The mixture was stirred overnight at room temperature. The mixture was washed with a saturated solution of NaHCO3 (300 mL) and water (300 mL) and dried over Na2SO4. The drying agent was removed by filtration and the solvents removed using a rotary evaporator. The residue was purified by chromatography on silica gel (120 g RediSep column, eluting with a gradient of 0% through 30% ethyl acetate/hexanes over 70 min, 85 mL/min) to give the product 32 (4.01 g, 81%) as a colorless liquid. The mixture was washed with a saturated solution of NaHCO3 (300 mL) and water (300 mL) dried over Na2SO4 The drying agent was removed by filtration the solvents removed a rotary evaporator The residue was purified by chromatography on silica gel (120 g RediSep column eluting with a gradient of 0% through 30% ethyl acetate/hexanes over 70 min

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

Procedure: To a solution of compound 30 (3.50 g, 12.9 mmol) and 4-methoxybenzyl trichloroacetimidate (4.65 g, 17.3 mmol) in DCM (100 mL) was added camphorsulfonic acid (450 mg, 1.92 mmol). The mixture was stirred overnight at room temperature. The mixture was washed with a saturated solution of NaHCO3 (300 mL) and water (300 mL) and dried over Na2SO4. The drying agent was removed by filtration and the solvents removed using a rotary evaporator. The residue was purified by chromatography on silica gel (120 g RediSep column, eluting with a gradient of 0% through 30% ethyl acetate/hexanes over 70 min, 85 mL/min) to give the product 32 (4.01 g, 81%) as a colorless liquid. The mixture was washed with a saturated solution of NaHCO3 (300 mL) and water (300 mL) dried over Na2SO4 The drying agent was removed by filtration the solvents removed a rotary evaporator The residue was purified by chromatography on silica gel (120 g RediSep column eluting with a gradient of 0% through 30% ethyl acetate/hexanes over 70 min

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

Procedure: Add lanthanum triflate (3.6 g, 6.16 mmol) to a solution of 2,2,2-trichloro-acetimidic acid 4-methoxybenzyl ester (52.2 g, 185 mmol) and (2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (30.2 g, 123 mmol) in toluene (200 mL). Stir 2.5 h, add methanol and concentrate. Dissolve in 25:75 dichloromethane:hexanes, filter away the insolubles and purify filtrate (silica gel chromatography, eluting with dichloromethane/ethyl acetate mixtures) to give the title compound (37.85 g, 84%). concentrate Dissolve in 25:75 dichloromethane hexanes, filter away the insolubles purify filtrate (silica gel chromatography, eluting with dichloromethane/ethyl acetate mixtures)

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

Procedure: Add lanthanum triflate (3.6 g, 6.16 mmol) to a solution of 2,2,2-trichloro-acetimidic acid 4-methoxybenzyl ester (52.2 g, 185 mmol) and (2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (30.2 g, 123 mmol) in toluene (200 mL). Stir 2.5 h, add methanol and concentrate. Dissolve in 25:75 dichloromethane:hexanes, filter away the insolubles and purify filtrate (silica gel chromatography, eluting with dichloromethane/ethyl acetate mixtures) to give the title compound (37.85 g, 84%). concentrate Dissolve in 25:75 dichloromethane hexanes, filter away the insolubles purify filtrate (silica gel chromatography, eluting with dichloromethane/ethyl acetate mixtures)

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

Procedure: Add a solution of 4-methoxybenzyl alcohol (31 mL, 250 mmol) in diethyl ether (250 ml) to sodium hydride (1.0 g, 25 mmol, 60% suspension in mineral oil) in diethyl ether (250 ml). Stir 30 min. Cool in ice bath and add trichloroacetonitrile (25 mL, 250 mmol) and let slowly warm to room temperature. Concentrate and dissolve in petroleum ether containing 0.3% methanol (330 mL) and filter through a filtering agent and concentrate to give the title compound (67 g, 95%). Cool in ice bath Concentrate dissolve in petroleum ether containing 0.3% methanol (330 mL) filter through a filtering agent concentrate

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2S)-tert-butyl 5-hydroxy-4-(hydroxymethyl)-2-(isopropyldimethylsilyl)oxy)methyl)-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 117, 13.0 g, 34.99 mmol) in toluene (150 mL) was added 4-methoxybenzyl 2,2,2-trichloroacetimidate (7.65 mL, 10.42 g, 36.74 mmol) and La(OTf)3 (205 mg, 0.35 mmol). The mixture was stirred at 50° C. for 4 h. Aqueous work-up with ethyl acetate and the organic layer was dried over MgSO4 to afford the crude product. Aqueous work-up with ethyl acetate and the organic layer was dried over MgSO4

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (2S)-tert-butyl 5-hydroxy-4-(hydroxymethyl)-2-(isopropyldimethylsilyl)oxy)methyl)-5,6-dihydropyridine-1(2H)-carboxylate (Intermediate 117, 13.0 g, 34.99 mmol) in toluene (150 mL) was added 4-methoxybenzyl 2,2,2-trichloroacetimidate (7.65 mL, 10.42 g, 36.74 mmol) and La(OTf)3 (205 mg, 0.35 mmol). The mixture was stirred at 50° C. for 4 h. Aqueous work-up with ethyl acetate and the organic layer was dried over MgSO4 to afford the crude product. Aqueous work-up with ethyl acetate and the organic layer was dried over MgSO4

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