Glutamic acid diethyl ester hydrochloride → 2-[(5-Bromo-3-methyl-thiophene-2-carbonyl)-amino]-glutamic acid diethyl ester

HRID 1532973Notes

Reaction equation

HRID 1532973 reaction equation
[Br:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[C:4]([CH3:10])[CH:3]=1.O.O[N:13]1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.Cl.[CH2:32]([O:34][C:35](=[O:45])[C@H:36]([CH2:38][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[NH2:37])[CH3:33].Cl.CN(C)CCCN=C=NCC>CN(C=O)C.O>[CH2:32]([O:34][C:35](=[O:45])[C@:36]([NH:13][C:7]([C:5]1[S:6][C:2]([Br:1])=[CH:3][C:4]=1[CH3:10])=[O:9])([CH2:38][CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[NH2:37])[CH3:33]

Participants

8

Reactant 5

HCID 73960Glutamic acid diethyl ester hydrochlorideHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 181766635-Bromo-3-methylthiophene-2-carboxylic acid

Product 1

HCID 701466202-[(5-Bromo-3-methyl-thiophene-2-carbonyl)-amino]-glutamic acid diethyl esterYield 99%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 10.86 g (49.1 mmol) of 5-Bromo-3-methyl-thiophene-2-carboxylic acid (prepared according to D. Spinelli, JCS Perkin Trans. II, 1972, 1866), 6.97 g (51.6 mmol) of 1-Hydroxybenzotriazole hydrate, 9.0 mL (51.7 mmol) of diisopropylethylamine and 12.36 g (51.6 mmol) of L-glutamic acid diethyl ester hydrochloride in 70 mL of DMF was added 9.89 g (51.6 mmol) of 1-(3-Dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride. The reaction mixture was stirred under Argon for 18 hours, poured into H2O and extracted with ethyl acetate. The organic layer was washed sequentially with 0.5N HCl, saturated NaHCO3 soln and saturated NaCl soln, dried over MgSO4, then concentrated under reduced pressure. This residue was purified by flash chromatography on silica gel eluting methylene chloride-ethyl acetate (20:1). In this manner, there was obtained 19.70 g (99%) of the desired product as a colorless oil.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed sequentially with 0.5N HCl, saturated NaHCO3 soln
  3. dry with materialsaturated NaCl soln, dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThis residue was purified by flash chromatography on silica gel
  6. washeluting methylene chloride-ethyl acetate (20:1)

Sources & evidence

ORD record
ord-b5ea892ce3604b62975f8b1cceaf0d0b
Source dataset
uspto-grants-2001_03
Patent number
US06207670B1

Reaction notes

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