1-Methylimidazole → HCID 117678410, compound

HRID 931347Notes

Reaction equation

HRID 931347 reaction equation
[C:1]([NH:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])(=[O:3])[CH3:2].CN1C=CN=C1.[CH3:17][C:18]1[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=1[C:20](Cl)=[O:21].C(N(CCCC)CCCC)CCC>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[C:1]([NH:4][C@H:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[C:20](=[O:21])[C:19]1[CH:23]=[CH:24][CH:25]=[CH:26][C:18]=1[CH3:17])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 13901-MethylimidazoleHCID 7622TributylamineHCID 702762-Methylbenzoyl chlorideHCID 74702Ethyl acetamidoacetate

Product 1

HCID 117678410HCID 117678410, compound

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
-45 °C

Procedure

A solution of ethyl N-acetylglycinate (98%, 7.41 g, 50.0 mmol) and 1-methyl-1H-imidazole (99%, 4.81 mL, 60.0 mmol) in dichloromethane (100 mL) was cooled to −45° C. and treated with 2-methylbenzoyl chloride (99%, 6.59 mL, 50.0 mmol). The reaction was stirred at −45° C. for 10 minutes. Titanium(IV) chloride (19.2 mL, 175 mmol) was added, followed by tri-n-butylamine (98%, 48.6 mL, 200 mmol), and stirring was continued at the same temperature for 30 minutes. The reaction was quenched with water and extracted with diethyl ether; the combined organic layers were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo. Silica gel chromatography (Eluents: 1:5 ethyl acetate/heptane followed by 1:2 ethyl acetate/heptane) afforded the product. Yield: 6.00 g, 22.8 mmol, 46%. APCI m/z 264.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 7.93 (dd, J=7.8, 1.2 Hz, 1H), 7.44 (ddd, J=7.6, 7.5, 1.4 Hz, 1H), 7.26-7.34 (m, 2H), 6.89 (br d, J=7 Hz, 1H), 6.05 (d, J=7.2 Hz, 1H), 4.04-4.19 (m, 2H), 2.45 (br s, 3H), 2.11 (s, 3H), 1.06 (t, J=7.1 Hz, 3H).

Workup

  1. stirringstirring
  2. waitwas continued at the same temperature for 30 minutes
  3. customThe reaction was quenched with water
  4. extractionextracted with diethyl ether
  5. washthe combined organic layers were washed with saturated aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customSilica gel chromatography (Eluents: 1:5 ethyl acetate/heptane followed by 1:2 ethyl acetate/heptane) afforded the product

Sources & evidence

ORD record
ord-42ae5e3f83224254bafc934b97ad5226
Source dataset
uspto-grants-2016_03
Patent number
US09296761B2

Reaction notes

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