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

HRID 898892Notes

Reaction equation

HRID 898892 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:24]=[CH:23][CH:22]=[CH:21][C:6]=1[O:7][CH2:8][CH2:9][C:10]1[CH:20]=[CH:19][C:13]([O:14][CH2:15][C:16]([OH:18])=O)=[CH:12][CH:11]=1)=[O:4].[F:25][C:26]1[CH:35]=[CH:34][CH:33]=[CH:32][C:27]=1[CH2:28][NH:29][CH2:30][CH3:31].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH2:30]([N:29]([CH2:28][C:27]1[CH:32]=[CH:33][CH:34]=[CH:35][C:26]=1[F:25])[C:16](=[O:18])[CH2:15][O:14][C:13]1[CH:12]=[CH:11][C:10]([CH2:9][CH2:8][O:7][C:6]2[CH:21]=[CH:22][CH:23]=[CH:24][C:5]=2[C:3]([O:2][CH3:1])=[O:4])=[CH:20][CH:19]=1)[CH3:31]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 4719442Ethyl[(2-fluorophenyl)methyl]amineHCID 69258392(4-{2-[2-(Methoxycarbonyl)phenoxy]ethyl}phenoxy)acetic acid

Product 1

HCID 69259940Methyl 2-[2-(4-{2-[ethyl(2-fluorobenzyl)amino]-2-oxoethoxy}phenyl)ethoxy]benzoateYield 71.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(4-{2-[2-(Methoxycarbonyl)phenoxy]ethyl}phenoxy)acetic acid (0.200 mg, 0.605 mmol) was dissolved in DMF and cooled on an ice-bath N-(2-Fluorobenzyl) ethanamine (0.102 g, 0.666 mmol), TBTU (0.214 g, 0.666 mmol) and DIPEA (0.22 ml, 1.271 mmol) was added. The reaction mixture was stirred for 16 h at room temperature. EtOAc was added and the organic phase was washed with two portions of 20 ml NaCO3 (sat). The organic layer was dried with MgSO4 and the solvent was removed by evaporation. The crude was purified by preparative HPLC (starting with acetonitrile/buffer 60/40 and then increasing the acetonitrile concentration to 100% acetonitrile in 25 min, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M), column KR-100-7-C8, 50*500, flow 80 ml/min). 145 mg of the desired product was obtained after freeze drying (yield 71.1%).

Workup

  1. additionwas added
  2. washthe organic phase was washed with two portions of 20 ml NaCO3 (sat)
  3. dry with materialThe organic layer was dried with MgSO4
  4. customthe solvent was removed by evaporation
  5. customThe crude was purified by preparative HPLC (
  6. temperatureincreasing
  7. concentrationthe acetonitrile concentration to 100% acetonitrile in 25 min
  8. additiona mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M), column KR-100-7-C8, 50*500, flow 80 ml/min)

Sources & evidence

ORD record
ord-c8d3977977e44c71a6b524f596f260e2
Source dataset
uspto-grants-2008_04
Patent number
US07351858B2

Reaction notes

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