1,2-Dibromoethane → 2-[3-Ethyl-4-(2-nitrobenzenesulfonyl)-2-oxo-piperazin-1-yl]-3-naphthalen-2-yl-propionic acid methyl ester

HRID 720175Notes

Reaction equation

HRID 720175 reaction equation
[CH3:1][O:2][C:3](=[O:35])[CH:4]([NH:16][C:17](=[O:34])[CH:18]([NH:21][S:22]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[N+:31]([O-:33])=[O:32])(=[O:24])=[O:23])[CH2:19][CH3:20])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1.Br[CH2:37][CH2:38]Br.C(=O)([O-])[O-].[K+].[K+].OS([O-])(=O)=O.[K+]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:35])[CH:4]([N:16]1[CH2:38][CH2:37][N:21]([S:22]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[N+:31]([O-:33])=[O:32])(=[O:24])=[O:23])[CH:18]([CH2:19][CH3:20])[C:17]1=[O:34])[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 78391,2-DibromoethaneHCID 11430Potassium CarbonateHCID 516920Potassium bisulfateHCID 695877123-Naphthalen-2-yl-2-[2-(2-nitrobenzenesulfonylamino)-butyryl amino]-propionic acid methyl ester

Product 1

HCID 695877642-[3-Ethyl-4-(2-nitrobenzenesulfonyl)-2-oxo-piperazin-1-yl]-3-naphthalen-2-yl-propionic acid methyl esterYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 3-naphthalen-2-yl-2-[2-(2-nitrobenzenesulfonylamino)-butyryl amino]-propionic acid methyl ester, 31, (26.6 g, 53.2 mmol) in anhydrous DMF (100 mL) is added 1,2-dibromoethane (100.0 g, 532.0 mmol) and potassium carbonate (66.1 g, 479.0 mmol). The reaction mixture is heated at 60° C. over night. The reaction mixture is cooled in an ice bath and the pH is adjusted to ˜3 with 1M KHSO4. The reaction mixture is extracted with EtOAc (3×300 mL). The organic layers are combined and washed with water (200 mL), dried over Na2SO4 and concentrated in vacuo and the resulting residue is purified over silica (Hexane: EtOAc 1:1; 5% MeOH in EtOAc) to afford 27.4 g (98% yield) of the desired product. 1H NMR (CDCl3, δ): 8.02–7.90 (m, 1H), 7.84–7.70 (m, 3H), 7.64–7.58 (m, 3H), 7.55–7.50 (m, 1H), 7.50–7.40 (m, 2H), 7.30 (d, J=6.0 Hz, 1H), 5.35 (dd, J−12.0, 4.8 Hz, 1H), 4.25 (t, J=7.2 Hz, 1H, 3.78–3.68 (m, 1H), 3.65 (s, 3H), 3.52 (dd, J=15.0, 6.0 Hz, 1H), 3.30–3.10 (m, 4H), 1.58–1.50 (m, 1H), 1.42–1.38 (m, 1H), 0.56 (t, J=7.2 Hz, 3H); 13C NMR, δ 170.5, 167.8, 148.0, 134.2, 134.0, 133.6, 133.1, 132.6, 132.3, 130.9, 128.5, 127.9, 127.7, 127.5, 126.9, 126.5, 126.0, 124.6.

Workup

  1. temperatureThe reaction mixture is cooled in an ice bath
  2. extractionThe reaction mixture is extracted with EtOAc (3×300 mL)
  3. washwashed with water (200 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customthe resulting residue is purified over silica (Hexane: EtOAc 1:1; 5% MeOH in EtOAc)

Sources & evidence

ORD record
ord-e1b78f5593064a028f938fec8f15db24
Source dataset
uspto-grants-2006_11
Patent number
US07132539B2

Reaction notes

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