Potassium Carbonate → 4-Bromo-3-{[(2,4-dimethoxy-benzyl)-methoxycarbonylmethyl-amino]-methyl}-thiophene-2-carboxylic acid methyl ester

HRID 1465950Notes

Reaction equation

HRID 1465950 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][CH:7]=[C:8]([Br:12])[C:9]=1[CH2:10]Br)=[O:4].[CH2:13]([O:15][C:16](=[O:30])[CH2:17][NH:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:21]=1[O:28][CH3:29])C.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][CH:7]=[C:8]([Br:12])[C:9]=1[CH2:10][N:18]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:21]=1[O:28][CH3:29])[CH2:17][C:16]([O:15][CH3:13])=[O:30])=[O:4]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 19895532Ethyl 2-(2,4-dimethoxybenzylamino)acetateHCID 67233904Methyl 4-bromo-3-(bromomethyl)thiophene-2-carboxylate

Product 1

HCID 672333554-Bromo-3-{[(2,4-dimethoxy-benzyl)-methoxycarbonylmethyl-amino]-methyl}-thiophene-2-carboxylic acid methyl esterYield 92.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-Bromo-3-bromomethyl-thiophene-2-carboxylic acid methyl ester (2.28 g, 7.31 mmol), example 31-b, was dissolved in 18 mL of dry N,N-dimethylformamide. N-(2,4-dimethoxy-benzyl)glycine ethyl ester (1.75 g, 7.31 mmol) and potassium carbonate (1.11 g, 8.04 mmol) were added and the reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organic fraction 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 3.18 g of a tan oil. MS: (+) m/z 494.1, 496.1 (M+Na+, 79Br/81Br).

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic fraction was dried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography
  5. washeluting from silica gel with a gradient of 0-60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-287ef8af6cc34f0eabbf9e7b2488d232
Source dataset
uspto-grants-2015_04
Patent number
US09000006B2

Reaction notes

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