1,2-Dichloroethane → benzyl N-[4-[[[2-(2,6-difluoro-3-hydroxyphenyl)-2-ethoxyacetyl]amino]methyl]benzenecarboximidoyl]carbamate

HRID 1247383Notes

Reaction equation

HRID 1247383 reaction equation
[F:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[C:4]([F:9])[C:3]=1[CH:10]([O:14][CH2:15][CH3:16])[C:11]([OH:13])=O.Cl.Cl.[CH2:19]([O:26][C:27](=[O:39])[NH:28][C:29]([C:31]1[CH:36]=[CH:35][C:34]([CH2:37][NH2:38])=[CH:33][CH:32]=1)=[NH:30])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.ON1C2C=CC=CC=2N=N1.C(Cl)CCl>CN(C=O)C.C(N(CC)CC)C>[CH2:19]([O:26][C:27](=[O:39])[NH:28][C:29]([C:31]1[CH:32]=[CH:33][C:34]([CH2:37][NH:38][C:11](=[O:13])[CH:10]([C:3]2[C:4]([F:9])=[CH:5][CH:6]=[C:7]([OH:8])[C:2]=2[F:1])[O:14][CH2:15][CH3:16])=[CH:35][CH:36]=1)=[NH:30])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 21905416(RS)-(2,6-difluoro-3-hydroxy-phenyl)-ethoxy-acetic acidHCID 141089245Carbamic acid, [[4-(aminomethyl)phenyl]iminomethyl]-, phenylmethyl ester, dihydrochloride

Product 1

HCID 140474512benzyl N-[4-[[[2-(2,6-difluoro-3-hydroxyphenyl)-2-ethoxyacetyl]amino]methyl]benzenecarboximidoyl]carbamateYield 40.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of (RS)-(2,6-difluoro-3-hydroxy-phenyl)-ethoxy-acetic acid (12.0 g) in DMF (600 ml) was added [(4-aminomethyl-phenyl)-imino-methyl]-carbamic acid benzyl ester dihydrochloride [Prepared according to Ch. Lila, Ph. Gloanec, L. Cadet, Y. Hervé, J. Fournier, F. Leborgne, T. J. Verbeuren, G. De Nanteuil, Synthetic Communications 1998, 28, 23, 4419–4429] (18.2 g) and 1-hydroxybenzotriazole. The mixture was cooled to 0–5° C. and EDC (15.8 g) and trietylamine (62 ml) were added. The mixture was stirred 1 h at 0–5° C. and over night at rt. The solvent was evaporated and the residue was dissolved in CH2Cl2 and washed with H2O (600 ml), and brine (300 ml). The aqueous layers were extracted with more CH2Cl2 (2×300 ml). The combined organic layers were dried (Na2SO4) and the solvent was evaporated. CC(CH2Cl2/2 N NH3 in MeOH 97:3 to 19:1) afforded 10.2 g (40%) of (RS)-[(4-{[2-(2,6-difluoro-3-hydroxy-phenyl)-2-ethoxy-acetylamino]-methyl}-phenyl)-imino-methyl]-carbamic acid benzyl ester. White foam. MS 498.2 ([M+H]+).

Workup

  1. temperatureThe mixture was cooled to 0–5° C.
  2. customThe solvent was evaporated
  3. dissolutionthe residue was dissolved in CH2Cl2
  4. washwashed with H2O (600 ml), and brine (300 ml)
  5. extractionThe aqueous layers were extracted with more CH2Cl2 (2×300 ml)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. customthe solvent was evaporated

Sources & evidence

ORD record
ord-77f1184b34e74822b2b5e9117108ebd0
Source dataset
uspto-grants-2006_10
Patent number
US07129238B2

Reaction notes

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