Benzene → HCID 54349115, compound

HRID 1108288Notes

Reaction equation

HRID 1108288 reaction equation
[Br:1][C:2]1[S:3]C=C(C(O)=O)[N:6]=1.S(Cl)(Cl)=[O:11].[CH2:14]([O:16][C:17](=[O:27])[C@H:18]([CH2:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[NH2:19])[CH3:15].C(N(CC)CC)C.[CH:35]1[CH:40]=CC=C[CH:36]=1>C(Cl)Cl.CN(C1C=CC=CN=1)C.CN(C)C=O>[CH2:14]([O:16][C:17](=[O:27])[C@H:18]([CH2:20][CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23])[NH:19][C:36]([C:35]1[S:3][C:2]([Br:1])=[N:6][CH:40]=1)=[O:11])[CH3:15]

Participants

9

Reactant 5

HCID 241BenzeneHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 73961Glutamic acid diethyl esterHCID 27632092-Bromo-1,3-thiazole-4-carboxylic acid

Product 1

HCID 54349115HCID 54349115, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 218852-DimethylaminopyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a 100 mL 14/20 round bottom flask under a nitrogen atmosphere was charged 1.0 g (4.81 mmmol) of 2-bromo-4-thiazolecarboxylic acid in 10 mL of benzene, followed by the addition of 1.4 mL (19 mmol) of thionyl chloride, and a catalytic amount of dimethylformamide. The reaction was heated to reflux for 2 hours The volatiles were removed in vacuo, and this residue was then dissolved in 15 mL of methylene chloride and added dropwise to an ice-bath cooled mixture of 1.21 g (5.05 mmol) of L-glutamic acid diethyl ester, 1.41 mL (10.1 mmol) of triethylamine, and 5 mg of dimethylaminopyridine in 15 mL methylene chloride. After the addition, the ice bath was removed and the reaction was stirred at room temperature for 2 hours The reaction was diluted with methylene chloride, washed with 0.1 N hydrochloric acid, water, 5% sodium bicarbonate, water, dried over sodium sulfate, and removed in vacuo. The crude residue was purified using silica gel flash chromatography eluting with a gradient of 1:2 ethyl acetate/hexanes to 1:1 ethyl acetate/hexanes to give 0.9 g (48%) of N-[(2-bromo-5-thiazolyl)carbonyl]-L-glutamic acid diethyl ester as a yellow oil. Rf =0.30 (1:2 ethyl acetate/hexanes), 1H NMR (300 MHz, CDCl3) δ 1.24-1.34 (m, 6H), 2.15-2.32 (m, 2H), 2.47-2.55 (m, 2H), 4.12-4.30 (m, 4H), 4.64-4.71 (m, 1H), 7.97 (s, 1H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 2 hours The volatiles
  3. customwere removed in vacuo
  4. dissolutionthis residue was then dissolved in 15 mL of methylene chloride
  5. additionadded dropwise to an ice-bath
  6. temperaturecooled
  7. additionAfter the addition
  8. customthe ice bath was removed
  9. additionwas diluted with methylene chloride
  10. washwashed with 0.1 N hydrochloric acid, water, 5% sodium bicarbonate, water
  11. dry with materialdried over sodium sulfate
  12. customremoved in vacuo
  13. customThe crude residue was purified
  14. washeluting with a gradient of 1:2 ethyl acetate/hexanes to 1:1 ethyl acetate/hexanes

Sources & evidence

ORD record
ord-3c398945ca804b98b7637214e52769b1
Source dataset
uspto-grants-2000_05
Patent number
US06066639

Reaction notes

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