Diisopropylethylamine → Ethyl 2-(4-(4-(4-(1,1-dimethylethoxycarbonyl)piperazin-1-yl)phenylcarbonylamino)-3-methylphenoxy)acetate

HRID 1459413Notes

Reaction equation

HRID 1459413 reaction equation
[CH3:1][C:2]([CH3:22])([O:4][C:5]([N:7]1[CH2:12][CH2:11][N:10]([C:13]2[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=2)[CH2:9][CH2:8]1)=[O:6])[CH3:3].Cl.[NH2:24][C:25]1[CH:37]=[CH:36][C:28]([O:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:27][C:26]=1[CH3:38].C1CCN(C(Cl)=[N+]2CCCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>C(Cl)(Cl)Cl.C(Cl)Cl>[CH3:3][C:2]([CH3:22])([O:4][C:5]([N:7]1[CH2:8][CH2:9][N:10]([C:13]2[CH:14]=[CH:15][C:16]([C:17]([NH:24][C:25]3[CH:37]=[CH:36][C:28]([O:29][CH2:30][C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:27][C:26]=3[CH3:38])=[O:18])=[CH:20][CH:21]=2)[CH2:11][CH2:12]1)=[O:6])[CH3:1]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27955084-[4-(tert-Butoxycarbonyl)piperazin-1-yl]benzoic acidHCID 15429165Chlorodipiperidinocarbenium hexafluorophosphateHCID 70346506Acetic acid,(4-amino-3-methylphenoxy)-,ethyl ester hydrochloride

Product 1

HCID 54494373Ethyl 2-(4-(4-(4-(1,1-dimethylethoxycarbonyl)piperazin-1-yl)phenylcarbonylamino)-3-methylphenoxy)acetateYield 100.1%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a 100 mL round bottomed flask with a stirring bar and an argon inlet was added 4-(4-(1,1-dimethylethoxycarbonyl) piperazinyl)benzoic acid (0.75 g, 2.45 mmol), ethyl 4-amino-3-methylphenoxyacetate hydrochloride (0.60 g, 2.45 mmol), chloro-N,N,N',N',-bis(pentamethylene)formamidinium hexafluorophosphate (0.97 g, 2.69 mmol), and CH2Cl2 (30 mL). This mixture was cooled in an ice bath and diisopropylethylamine (1.74 mL, 10.0 mmol) was added. The ice bath was allowed to expire and the solution was stirred at ambient temperature for 48 h. The solution was diluted with CHCl3 and washed with 10% aqueous citric acid, saturated aqueous NaHCO3, and brine. Drying (MgSO4), filtration and removal of the solvent in vacuo gave an oil. This material was chromatographed on 75 g of silica gel using 50% EtOAc-hexane as eluant. There was obtained 1.22 g (100%) of ethyl 2-(4-(4-(4-(1,1-dimethylethoxycarbonyl)piperazin-1-yl)phenylcarbonylamino)-3-methylphenoxy)acetate as a crystalline solid.

Workup

  1. temperatureThis mixture was cooled in an ice bath
  2. washwashed with 10% aqueous citric acid, saturated aqueous NaHCO3, and brine
  3. customDrying
  4. filtration(MgSO4), filtration and removal of the solvent in vacuo
  5. customgave an oil
  6. customThis material was chromatographed on 75 g of silica gel using 50% EtOAc-hexane as eluant

Sources & evidence

ORD record
ord-cfcac2ee88514dd5a9b52f876acab767
Source dataset
uspto-grants-1998_12
Patent number
US05854245

Reaction notes

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