Hydrochloric Acid → 2-(3-Ethyl-piperazin-1-yl)-3-naphthalen-2-yl-propionic acid methyl ester

HRID 720177Notes

Reaction equation

HRID 720177 reaction equation
[CH3:1][O:2][C:3](=[O:36])[CH:4]([N:16]1[CH2:21][CH2:20][N:19](S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)[CH:18]([CH2:34][CH3:35])[CH2:17]1)[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.C(=O)([O-])[O-].[K+].[K+].SC1C=CC(O)=CC=1.Cl>CN(C=O)C>[CH3:1][O:2][C:3](=[O:36])[CH:4]([N:16]1[CH2:21][CH2:20][NH:19][CH:18]([CH2:34][CH3:35])[CH2:17]1)[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 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2401474-MercaptophenolHCID 695877212-[3-Ethyl-4-(2-nitro-benzenesulfonyl)-piperazin-1-yl]-3-naphthalen-2-yl-propionic acid methyl ester

Product 1

HCID 695875432-(3-Ethyl-piperazin-1-yl)-3-naphthalen-2-yl-propionic acid methyl esterYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-[3-ethyl-4-(2-nitro-benzenesulfonyl)-piperazin-1-yl]-3-naphthalen-2-yl-propionic acid methyl ester, 33, (4.1 g, 8.0 mmol) in anhydrous DMF (40 mL) is added potassium carbonate (6.7 g, 48.2 mmol) and 4-mercaptophenol (3.0 g, 24.1 mmol). The reaction mixture is stirred for six hours at room temperature, cooled in a ice bath and the pH adjusted to ˜3 with 1M HCl. The reaction mixture is extracted with Et2O (4×100 mL), the organic layers combined and extracted with 1M HCl (100 mL). The organic layers are then discarded. The aqueous layers were combined and cooled in ice bath and pH was adjusted to ˜10 with K2CO3. The aqueous layer is extracted with EtOAc (4×125 mL) and dried over Na2SO4. The combined organic layers are concentrated in vacuo to afford 2.1 g (80% yield) of the desired product. 1H NMR (CDCl3, δ): 7.84–7.75 (m, 3H), 7.70 (s, 1H), 7.50–7.38 (m, 2H), 7.35 (dd, J=8.3, 1.7 Hz, 1H), 3.60(s, 3H), 3.55–3.50 (m, 1H), 3.30–3.24 (m, 1H), 3.18–3.08 (m, 1H), 3.05–2.75 (m, 5H), 2.70–2.55 (m, 1H), 2.50 (dd, J=10.4, 4.1 Hz, 1H), 2.04 (t, J=10.4 Hz, 1H), 1.52–1.32 (M, 2H), 1.00 (t, J=8.3 Hz, 3H); 13C NMR, δ 171.8, 135.9, 133.7, 132.4, 128.1, 128.0, 127.9, 127.8, 126.1, 125.6, 120.8, 70.0, 57.3, 54.3, 52.9, 51.3, 46.4, 35.7, 27.5, 10.6.

Workup

  1. temperaturecooled in a ice bath
  2. extractionThe reaction mixture is extracted with Et2O (4×100 mL)
  3. extractionextracted with 1M HCl (100 mL)
  4. temperaturecooled in ice bath
  5. extractionThe aqueous layer is extracted with EtOAc (4×125 mL)
  6. dry with materialdried over Na2SO4
  7. concentrationThe combined organic layers are concentrated in vacuo

Sources & evidence

ORD record
ord-e8ff40c99c7e4897a73e8afec2bd72a0
Source dataset
uspto-grants-2006_11
Patent number
US07132539B2

Reaction notes

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