Pyridine → 2-(2,2-Dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-N-(4-fluoro-benzyl)-N-methoxy-acetamide

HRID 2214543Notes

Reaction equation

HRID 2214543 reaction equation
[CH3:1][C:2]1([CH3:12])[O:6][C:5](=[CH:7][C:8](Cl)=[O:9])[C:4](=[O:11])[O:3]1.[F:13][C:14]1[CH:23]=[CH:22][C:17]([CH2:18][NH:19][O:20][CH3:21])=[CH:16][CH:15]=1.N1C=CC=CC=1>ClCCl>[CH3:1][C:2]1([CH3:12])[O:6][C:5](=[CH:7][C:8]([N:19]([CH2:18][C:17]2[CH:22]=[CH:23][C:14]([F:13])=[CH:15][CH:16]=2)[O:20][CH3:21])=[O:9])[C:4](=[O:11])[O:3]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 12147060Benzenemethanamine, 4-fluoro-N-methoxy-HCID 85435482(2,2-Dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-acetyl chloride

Product 1

HCID 730332332-(2,2-Dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-N-(4-fluoro-benzyl)-N-methoxy-acetamideYield 93.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
22 °C

Procedure

A solution of (2,2-dimethyl-5-oxo-[1,3]dioxolan-4-ylidene)-acetyl chloride (2.45 g, 12.9 mmol) in dichloromethane (15 ml) was added dropwise over 10 minutes to a cold (0–5° C.) mixture of N-4-fluorobenzyl-O-methyl-hydroxylamine (2.0 g, 12.9 mmol) and pyridine (2.1 ml, 25.7 mmol) in dichloromethane (50 ml). The cooling bath was then removed and the solution was stirred at 22° C. for 30 minutes. The reaction mixture was then quenched by the addition of water and ethyl acetate. The organic phase was washed successively with 0.1 N hydrochloric acid, saturated sodium bicarbonate, brine and dried (magnesium sulfate). Evaporation of the solvent and chromatography of the residue on silica gel (toluene-ethyl acetate, 8:2) gave 3.72 g (93% yield) of the title amide as white crystals: mp 111° C. (ethyl acetate-hexane). 1HNMR 400 MHz (CDCl3) δ (ppm): 1.75 (6H, s), 3.68 (3H, s), 4.79 (2H, s), 6.38 (1H, s), 7.0 (2H, m), 7.34 (2H, m). Anal. calcd for C15H16FNO5: C, 58.25; H, 5.21; N, 4.52. Found: C, 58.33; H, 5.38; N, 4.51.

Workup

  1. customThe cooling bath was then removed
  2. customThe reaction mixture was then quenched by the addition of water and ethyl acetate
  3. washThe organic phase was washed successively with 0.1 N hydrochloric acid, saturated sodium bicarbonate, brine
  4. dry with materialdried (magnesium sulfate)
  5. customEvaporation of the solvent and chromatography of the residue on silica gel (toluene-ethyl acetate, 8:2)

Sources & evidence

ORD record
ord-d25c9d63c9ae46ae848fe1ab0f32e3cf
Source dataset
uspto-grants-2006_09
Patent number
US07109186B2

Reaction notes

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