Dicyclohexylcarbodiimide → 4-(2-Benzyloxyacetylamino)phenoxyacetic acid methyl ester

HRID 83813

Reaction equation

HRID 83813 reaction equation
[CH3:1][O:2][C:3](=[O:13])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][CH:7]=1.[CH2:14]([O:21][CH2:22][C:23](O)=[O:24])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C1(N=C=NC2CCCCC2)CCCCC1>ClCCl>[CH3:1][O:2][C:3](=[O:13])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:23](=[O:24])[CH2:22][O:21][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:8][CH:7]=1

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 290301(Benzyloxy)acetic acidHCID 6422115Methyl(4-aminophenoxy)acetate

Product 1

HCID 592539834-(2-Benzyloxyacetylamino)phenoxyacetic acid methyl esterYield 68.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of (4-aminophenoxy)-acetic acid methyl ester 3 (20 g, 110.5 mmol) and benzyloxy acetic acid (20.4 g, 123 mmol) in anhydrous dichloromethane (200 ml) under nitrogen atmosphere was added dropwise a solution of 1,3-dicyclohexyl carbo-diimide (63.2 g, 306 mmol) in anhydrous dichloromethane (80 ml) then stirred at room temp. for 12 hours. The solids were filtered off, the dichloromethane was washed with 5% sodium bicarbonate solution (100 ml), water (100 ml) added, and the solids dried over sodium sulphate and distilled to get crude 49. Crude 49 was purified by column chromatography on silica gel using benzene as eluant to get pure 49 (25 g, 68.9%) as a white powder with an m.p. between 76-77.5° C. 1H NMR (CDCl3) δ 3.82 (s, 3H, ester), 4.10 (s, 2H, CH2), 4.62 (s, 2H, CH2), 4.66 (s, 2H, CH2), 6.88 (d, 2H, Ar), 7.38 (m, 5H, Ar), 7.46 (d, 2H, Ar), 8.24 (bs, 1H, NH)

Workup

  1. filtrationThe solids were filtered off
  2. washthe dichloromethane was washed with 5% sodium bicarbonate solution (100 ml), water (100 ml)
  3. additionadded
  4. dry with materialthe solids dried over sodium sulphate
  5. distillationdistilled
  6. customto get crude 49
  7. customCrude 49 was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-c57186fa43784b8e8a50548a6a12cdb3
Source dataset
uspto-grants-2014_09
Patent number
US08846845B2

Linked notes

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