Hydrochloric Acid → (S)-1-[N-(3,5-Dichlorophenyl)-N-phenylcarbamoyl]-4-(N,N-di-n-pentylcarbamoyl)piperazine-2-carboxylic acid

HRID 2226040Notes

Reaction equation

HRID 2226040 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][C@H:13]2[C:18]([OH:20])=[O:19])=[O:11])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH2:27]([N:32]([CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[C:33](Cl)=[O:34])[CH2:28][CH2:29][CH2:30][CH3:31].C(N(CC)CC)C.Cl>C1COCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]([N:12]2[CH2:17][CH2:16][N:15]([C:33](=[O:34])[N:32]([CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH2:14][C@H:13]2[C:18]([OH:20])=[O:19])=[O:11])[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 8471Triethylamine2×HCID 22106956Dipentylcarbamyl chloride2×HCID 54121325(S)-1-[N-(3,5-Dichlorophenyl)-N-phenylcarbamoyl]piperazine-2-carboxylic acid2×

Product 1

HCID 54538500(S)-1-[N-(3,5-Dichlorophenyl)-N-phenylcarbamoyl]-4-(N,N-di-n-pentylcarbamoyl)piperazine-2-carboxylic acidYield 54.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

A mixture of 470 mg (1.19 mmole) of (S)-1-[N-(3,5-dichlorophenyl)-N-phenylcarbamoyl]piperazine-2-carboxylic acid (from Step E above), 393 mg (1.79 mmole) of N,N-di-n-pentylcarbamoyl chloride (from Example 1, Step C-2) and 578 mg (4.17 mmole) of triethylamine in 15 mL of THF and 8 mL of water was stirred at 55° C. for 24 hours. The mixture was cooled and treated with 16 mL of 0.5N aqueous hydrochloric acid, and the aqueous layer was extracted with 3×55 mL of ethyl acetate. The combined organic extracts piperazine-2-carboxylic acid (from Step E above), 393 mg (1.79 mmole) of N,N-di-n-pentylcarbamoyl chloride (from Example 1, Step C-2) and 578 mg (4.17 mmole) of triethylamine in 15 mL of THF and 8 mL of water was stirred at 55° C. for 24 hours. The mixture was cooled and treated with 16 mL of 0.5N aqueous hydrochloric acid, and the aqueous layer was extracted with 3×55 mL of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on 120 g of silica eluting with 1 L of 100:3 methylene chloride:methanol then 1 L of 100:4.5:0.15 methylene chloride:methanol: acetic acid to give 374 mg (54%) of an oil.

Workup

  1. temperatureThe mixture was cooled
  2. extractionthe aqueous layer was extracted with 3×55 mL of ethyl acetate
  3. temperatureThe mixture was cooled
  4. extractionthe aqueous layer was extracted with 3×55 mL of ethyl acetate
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography on 120 g of silica eluting with 1 L of 100:3 methylene chloride

Sources & evidence

ORD record
ord-102e361546b740beb18dbd991daace9c
Source dataset
uspto-grants-1994_09
Patent number
US05344830

Reaction notes

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