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

HRID 898917Notes

Reaction equation

HRID 898917 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].[CH2:25]([NH:32][CH2:33][CH3:34])[C:26]1[CH:31]=[CH:30][CH:29]=[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>[CH2:25]([N:32]([CH2:33][CH3:34])[C:20](=[O:22])[CH2:19][O:18][C:17]1[CH:16]=[CH:15][C:14]([CH2:13][CH2:12][S:11][C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[C:3]([O:2][CH3:1])=[O:4])=[CH:24][CH:23]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 84352N-EthylbenzylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 57640312[4-(2-{[2-(Methoxycarbonyl)phenyl]thio}ethyl)phenoxy]acetic acid

Product 1

HCID 69258703Methyl 2-{[2-(4-{2-[benzyl(ethyl)amino]-2-oxoethoxy}phenyl)ethyl]thio}benzoateYield 51.2%

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-benzyl-N-ethylamine (0.086 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) was added. The solution was stirred over night 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 crude 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 0.137 g of methyl 2-{[2-(4-{2-[benzyl(ethyl)amino]-2-oxoethoxy}phenyl)-ethyl]thio}benzoate (yield 51.2%).

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 crude 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-d4e3d1732a734e51b4b4b948c84af558
Source dataset
uspto-grants-2008_04
Patent number
US07351858B2

Reaction notes

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