4-(Benzyloxy)benzoic acid → (4-Benzyloxy-benzoylamino)-acetic acid ethyl ester

HRID 1178062Notes

Reaction equation

HRID 1178062 reaction equation
CCN(C(C)C)C(C)C.[CH2:10]([O:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][CH:19]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[CH2:50]([O:52][C:53](=[O:56])[CH2:54][NH2:55])[CH3:51]>CN(C=O)C.O>[CH2:50]([O:52][C:53](=[O:56])[CH2:54][NH:55][C:22](=[O:24])[C:21]1[CH:20]=[CH:19][C:18]([O:17][CH2:10][C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=2)=[CH:26][CH:25]=1)[CH3:51]

Participants

8

Reactant 5

HCID 738804-(Benzyloxy)benzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2723640Glycine ethyl ester, hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 57855660(4-Benzyloxy-benzoylamino)-acetic acid ethyl esterYield 90.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (5.12 g, 6.85 mL, 0.59 mmol) was added to a stirred solution of 4-benzyloxy benzoic acid (2 g, 8.7 mmol) in DMF (18 mL). HOBT (1.3 g, 9.5 mmol) and EDCI.HCl (4.2 g, 21.7 mmol) were added at room temperature. After 2 minutes glycine ethyl ester HCl (1.47 g, 10.5 mmol) was added to the reaction mixture. The resulting mixture was stirred at room temperature overnight. Water was then added, and the product was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. Purification using column chromatography (silica gel of mesh size of 60-120 using 40% EtOAc in Hexane as eluent) afforded 2.47 g (90.1% yield) of (4-Benzyloxy-benzoylamino)-acetic acid ethyl ester. LCMS Purity %: 98.6, 1H NMR (DMSO): δ 8.9 (t, 1H), 7.8 (d, 2H), 7.5 (m, 5H), 7.2 (d, 2H), 5.4 (s, 2H), 4.2 (q, 2H), 4.0 (d, 2H), 0.8 (t, 3H).

Workup

  1. extractionthe product was extracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto afford the crude product
  6. customPurification

Sources & evidence

ORD record
ord-561bc1ddf12b4b8cae62ee656ad9f537
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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