Triethylamine → HCID 67232984, compound

HRID 1465946Notes

Reaction equation

HRID 1465946 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][O:8][C:9]([C:11]1[C:15]([Br:16])=[CH:14][S:13][C:12]=1[C:17]([OH:19])=O)=[O:10].[CH3:20][O:21][C:22]([C:24]1[S:25][CH:26]=[C:27]([Br:32])[C:28]=1[C:29]([OH:31])=O)=[O:23].C(N(CC)CC)C.Cl.[CH2:41]([O:43][C:44](=[O:47])[CH2:45][NH2:46])[CH3:42]>O1CCCC1.C(OCC)(=O)C.CN(C)C=O>[CH3:7][O:8][C:9]([C:11]1[C:15]([Br:16])=[CH:14][S:13][C:12]=1[C:17](=[O:19])[NH:46][CH2:45][C:44]([O:43][CH2:41][CH3:42])=[O:47])=[O:10].[CH3:20][O:21][C:22]([C:24]1[S:25][CH:26]=[C:27]([Br:32])[C:28]=1[C:29](=[O:31])[NH:46][CH2:45][C:44]([O:43][CH2:41][CH3:42])=[O:47])=[O:23]

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 2723640Glycine ethyl ester, hydrochlorideHCID 67232935HCID 67232935, compoundHCID 67233776HCID 67233776, compound

Product 2

HCID 67232984HCID 67232984, compoundHCID 67234723HCID 67234723, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

N,N-Dimethylformamide (13 μL) was added to a solution of oxalyl chloride (0.696 mL, 7.97 mmol), 4-bromo-thiophene-2,3-dicarboxylic acid 3-methyl ester and 4-bromo-thiophene-2,3-dicarboxylic acid 2-methyl ester (1.41 g, 5.32 mmol), example 30-c, in tetrahydrofuran (6.4 mL) at 0° C. The reaction mixture was stirred at 0° C. for 15 min, and then at ambient temperature for 1 h. After the reaction mixture was concentrated and dried under hi-vacuum, the residue was dissolved in 1,4-dioxane (2.5 mL) and cooled to 0° C. with an external ice bath. Triethylamine (2.22 mL, 16.0 mmol) and glycine ethyl ester hydrochloride salt (1.11 g, 7.97 mmol) were added slowly to the cold solution. The reaction mixture was warmed to room temperature and stirred for 2.5 h. The reaction mixture was diluted with ethyl acetate and washed successively with 0.5 N HCl, water, saturated sodium bicarbonate solution and brine. The organic solution was dried over anhydrous sodium sulfate and concentrated. The crude product was purified by flash chromatography eluting from silica gel with a gradient of 0-60% ethyl acetate in hexanes to produce 1.0 g of 4-bromo-2-(ethoxycarbonylmethyl-carbamoyl)-thiophene-3-carboxylic acid methyl ester and 0.1 g of 4-bromo-3-(ethoxycarbonylmethyl-carbamoyl)-thiophene-2-carboxylic acid methyl ester. MS for 4-bromo-2-(ethoxycarbonylmethyl-carbamoyl)-thiophene-3-carboxylic acid methyl ester: (+) m/z 349.9, 351.9 (M+1, 79Br/81Br). MS for 4-bromo-3-(ethoxycarbonylmethyl-carbamoyl)-thiophene-2-carboxylic acid methyl ester: (+) m/z 349.9, 351.9 (M+1, 79Br/81Br).

Workup

  1. waitat ambient temperature for 1 h
  2. concentrationAfter the reaction mixture was concentrated
  3. customdried under hi-vacuum
  4. dissolutionthe residue was dissolved in 1,4-dioxane (2.5 mL)
  5. temperaturecooled to 0° C. with an external ice bath
  6. temperatureThe reaction mixture was warmed to room temperature
  7. stirringstirred for 2.5 h
  8. washwashed successively with 0.5 N HCl, water, saturated sodium bicarbonate solution and brine
  9. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customThe crude product was purified by flash chromatography
  12. washeluting from silica gel with a gradient of 0-60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-a406133c03a9421f9d06e2f7062ab737
Source dataset
uspto-grants-2015_04
Patent number
US09000006B2

Reaction notes

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