pent-4-enoyl chloride

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: Flush with nitrogen a 12 L 3-neck round bottom flask equipped with a mechanical stirrer, internal temperature probe/N2 inlet, and 1 L addition funnel for 20 min and then add (R)-4-benzyl-2-oxazolidinone (250 g, 1.41 mol). Dilute with tetrahydrofuran (THF) (1.8 L) and cool in a dry ice/acetone bath until the internal temperature is −74° C. Transfer a 1.6M hexanes solution of n-butyllithium (970 mL, 1.552 mol) to the addition funnel via cannula, and add to the oxazolidinone solution at a rate such that the internal temperature does not reach above −65° C. After the addition is complete, allow the reaction to stir in the cooling bath 30 min. Transfer 4-pentenoyl chloride (175 mL, 1.585 mol) to the addition funnel and add dropwise to the anion solution over a 25 min period. Stir the reaction for 45 min in the cooling bath. Remove the cooling bath and stir the reaction 18 hr as it slowly reaches room temperature. Dilute the mixture with 1N aqueous hydrochloric acid (1.5 L) and diethyl ether (1 L). Separate the layers and wash the organic phase with water (2×1 L) then brine (1 L). Extract the combined aqueous washes with ether (1 L). Dry the combined organic phases over anhydrous magnesium sulfate, filter, and concentrate to 390 g of a light tan oil. Purify this material by silica gel chromatography using hexanes:ethyl acetate to obtain 345 g (94.5%) of a clear, yellow oil. Flush with nitrogen a 12 L 3-neck round bottom flask equipped with a mechanical stirrer internal temperature probe/N2 inlet, and 1 L addition funnel for 20 min cool in a dry ice/acetone bath until the internal temperature is −74° C does not reach above −65° C After the addition the reaction Stir the reaction for 45 min in the cooling bath Remove the cooling bath stir the reaction 18 hr as it slowly reaches room temperature Separate the layers wash the organic phase with water (2×1 L) Extract the combined aqueous washes with ether (1 L) Dry the combined organic phases over anhydrous magnesium sulfate filter concentrate to 390 g of a light tan oil Purify this material by silica gel chromatography ethyl acetate to obtain 345 g (94.5%) of a clear, yellow oil

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

Procedure: To the product of Step A, 1-a, (5.10 g, 25.1 mmol) in CH2Cl2 (50 mL) was added pent-4-enoyl chloride (2.83 mL, 25.1 mmol, 98% purity) and NEt3 (4.20 mL, 30.1 mmol) at 5° C. The reaction stirred about 18 hours and was then diluted with CH2Cl2, washed with aq Na2CO3 (2 M) and brine, dried (Na2SO4), filtered and concentrated to afford the product, 1-b. washed with aq Na2CO3 (2 M) and brine dried (Na2SO4) filtered concentrated

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

Procedure: 4-Pentenoyl chloride (11.9 g, 100 mmol) was added to a stirred solution of N,N'-bis-[2-(acetyloxy) -1-[(acetyloxy)-methyl]ethyl]-5-amino-2,4,6-triiodo-1,3-benzenedicarboxamide (47.75 g, 50 mmol) in dimethylacetamide (400 mL) at room temperature and the mixture was stirred for 16 hours. Dimethylacetamide was removed in vacuo and the residue dissolved in ethyl acetate (600 ml). The solution was washed with aqueous sodium bicarbonate (10%, 2×150 mL) and with water (2×100 mL) and brine (150 mL). The organic layer was dried and the solvent removed to obtain the crude product as an off-white solid. Further purification by crystallization from a mixture of acetone (250 mL) and hexane (75 mL) afforded the title A compound (42.5 g), m.p. 162°-64°. TLC: Rf 0.55 in ethyl acetate. Mass Spectrum: m/z 956 (M+H)+, 830, 653. Dimethylacetamide was removed in vacuo the residue dissolved in ethyl acetate (600 ml) The solution was washed with aqueous sodium bicarbonate (10%, 2×150 mL) and with water (2×100 mL) and brine (150 mL) The organic layer was dried the solvent removed to obtain the crude product as an off-white solid Further purification by crystallization from a mixture of acetone (250 mL) and hexane (75 mL)

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

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

Procedure: 4-Pentenoyl chloride (11.9 g, 100 mmol) was added to a stirred solution of N,N'-bis-[2-(acetyloxy)-1-[(acetyloxy)-methyl]ethyl]-5-amino-2,4,6 -triiodo-1,3-benzenedicarboxamide (47.75 g, 50 mmol) in dimethylacetamide (400 mL) at room temperature and the mixture was stirred for 16 hours. Dimethylacetamide was removed in vacuo and the residue dissolved in ethyl acetate (600 ml). The solution was washed with aqueous sodium bicarbonate (10%, 2×150 mL) and with water (2×100 mL) and brine (150 mL). The organic layer was dried and the solvent removed to obtain the crude product as an off-white solid. Further purification by crystallization from a mixture of acetone (250 mL) and hexane (75 mL) afforded the title A compound (42.5 g), m.p. 162°-64°. TLC: Rf 0.55 in ethyl acetate. Mass Spectrum: m/z 956 (M+H)+, 830, 653. Dimethylacetamide was removed in vacuo the residue dissolved in ethyl acetate (600 ml) The solution was washed with aqueous sodium bicarbonate (10%, 2×150 mL) and with water (2×100 mL) and brine (150 mL) The organic layer was dried the solvent removed to obtain the crude product as an off-white solid Further purification by crystallization from a mixture of acetone (250 mL) and hexane (75 mL)