Dimethylformamide → Methyl 4-(2-amino-2-oxoethoxy)-2-methoxybenzoate

HRID 1688271Notes

Reaction equation

HRID 1688271 reaction equation
Br[CH2:2][C:3]([NH2:5])=[O:4].CN(C=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].[OH:17][C:18]1[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[C:20]([O:28][CH3:29])[CH:19]=1>C(Cl)Cl>[NH2:5][C:3](=[O:4])[CH2:2][O:17][C:18]1[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[C:20]([O:28][CH3:29])[CH:19]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 696322-BromoacetamideHCID 12532676Methyl 4-hydroxy-2-methoxybenzoate

Product 1

HCID 67211435Methyl 4-(2-amino-2-oxoethoxy)-2-methoxybenzoateYield 91.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a sealed tube was added 2-bromoacetamide (2.272 g, 16.47 mmol), DMF (50 mL), cesium carbonate (7.15 g, 21.96 mmol) and methyl 4-hydroxy-2-methoxybenzoate (1.00 g, 5.49 mmol). The tube was sealed and heated for 16 hours at 85° C. The reaction mixture was diluted with DCM, washed sequentially with 10 mL of 1M HCl, water, and brine. The solution was dried over sodium sulfate, filtered and the solvent removed to give 1.2 grams of methyl 4-(2-amino-2-oxoethoxy)-2-methoxybenzoate (78% yield) as a yellow powder. The LC/MS data was obtained on a Shimadzu analytical LC/Micromass Platform LC (ESI+) at 220 nm using the following set of conditions: Waters Sunfire 5 μm C18, 4.6×30 mm column, with a gradient of 0-100% B (B=90% HPLC grade methanol/0.1% trifluoroacetic acid/10% HPLC grade water), (A=90% HPLC grade water/0.1% trifluoroacetic acid/10% HPLC grade methanol), in 2 minutes with a 1 minute hold at a rate of 4 mL/minute. 1H NMR (400 MHz, THF-d8) δ ppm 3.71-3.76 (m, 3H), 3.80-3.84 (m, 3H), 4.45 (s, 2H), 6.56 (dd, J=8.66, 2.38 Hz, 1H), 6.65 (d, J=2.26 Hz, 1H), 6.77 (br. s., 1H), 6.92 (br. s., 1H), 7.75 (d, J=8.78 Hz, 1H). LCMS Rt=1.385 min., m/z 240.2 (M+H), 92% purity.

Workup

  1. customThe tube was sealed
  2. washwashed sequentially with 10 mL of 1M HCl, water, and brine
  3. dry with materialThe solution was dried over sodium sulfate
  4. filtrationfiltered
  5. customthe solvent removed

Sources & evidence

ORD record
ord-b5d964ded49e4971aa1bd115ec74634b
Source dataset
uspto-grants-2012_04
Patent number
US08148382B2

Reaction notes

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