Diisopropylethylamine → Methyl 2-{[2-(4-{2-[(4-chlorobenzyl)(ethyl)amino]-2-oxoethoxy}phenyl)ethyl]thio}benzoate

HRID 898902Notes

Reaction equation

HRID 898902 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11][CH2:12][CH2:13][C:14]1[CH:24]=[CH:23][C:17]([O:18][CH2:19][C:20]([OH:22])=O)=[CH:16][CH:15]=1)=[O:4].[Cl:25][C:26]1[CH:35]=[CH:34][C:29]([CH2:30][NH:31][CH2:32][CH3:33])=[CH:28][CH:27]=1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)C(C)C)C>CN(C=O)C.O>[Cl:25][C:26]1[CH:27]=[CH:28][C:29]([CH2:30][N:31]([CH2:32][CH3:33])[C:20](=[O:22])[CH2:19][O:18][C:17]2[CH:16]=[CH:15][C:14]([CH2:13][CH2:12][S:11][C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[C:3]([O:2][CH3:1])=[O:4])=[CH:24][CH:23]=2)=[CH:34][CH:35]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 580651N-Ethyl-4-chlorobenzylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57640312[4-(2-{[2-(Methoxycarbonyl)phenyl]thio}ethyl)phenoxy]acetic acid

Product 1

HCID 69258846Methyl 2-{[2-(4-{2-[(4-chlorobenzyl)(ethyl)amino]-2-oxoethoxy}phenyl)ethyl]thio}benzoateYield 29.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

[4-(2-{[2-(Methoxycarbonyl)phenyl]thio}ethyl)phenoxy]acetic acid (0.200 g, 0.577 mmol) was dissolved in DMF (10 ml), N-(4-chlorobenzyl)-N-ethylamine (0.108 g, 0.635 mmol) was added and the mixture was cooled to 0° C. N-[(1H-1,2,3-benzotriazol-1-yloxy)(dimethylamino)methylene]-N-methylmethanaminium tetrafluoroborate (0.204 g, 0.635 mmol) and N-ethyl-N,N-diisopropylamine (0.157 g, 1.212 mmol) were added. The solution was stirred overnight at room temperature. Water (100 ml) was added and the water phase was extracted with diethyl ether (3×20 ml). The organic phase was washed with Na2CO3 (3×20 ml, aq) and HCl (0.5 M, 2×, 10 ml). The organic layer was dried (MgSO4) and the solvent was removed by evaporation. The residue was purified by flash chromatography (started with isocratic heptane/EtOAc 30/70 and then the EtOAc concentration was increased to 100%, (silica gel 60 0.004-0.063 mm). The product containing fractions were pooled and the solvent was removed by evaporation to give 0.085 g of methyl 2-{[2-(4-{2-[(4-chlorobenzyl)(ethyl)amino]-2-oxoethoxy}phenyl)ethyl]thio}benzoate (yield 29.6%).

Workup

  1. extractionthe water phase was extracted with diethyl ether (3×20 ml)
  2. washThe organic phase was washed with Na2CO3 (3×20 ml, aq) and HCl (0.5 M, 2×, 10 ml)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. customthe solvent was removed by evaporation
  5. customThe residue was purified by flash chromatography (
  6. concentrationthe EtOAc concentration
  7. temperaturewas increased to 100%, (silica gel 60 0.004-0.063 mm)
  8. additionThe product containing fractions
  9. customthe solvent was removed by evaporation

Sources & evidence

ORD record
ord-eb58fd90fef241ddac0a1780bdf45f57
Source dataset
uspto-grants-2008_04
Patent number
US07351858B2

Reaction notes

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