Diisopropylethylamine → (S)-4-benzyl 1-tert-butyl 2-(4-(4-fluorophenoxy)phenylcarbamoyl)piperazine-1,4-dicarboxylate

HRID 1630293Notes

Reaction equation

HRID 1630293 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:13]([C:24](O)=[O:25])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:27][C:28]1[CH:41]=[CH:40][C:31]([O:32][C:33]2[CH:39]=[CH:38][C:36]([NH2:37])=[CH:35][CH:34]=2)=[CH:30][CH:29]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:27][C:28]1[CH:41]=[CH:40][C:31]([O:32][C:33]2[CH:39]=[CH:38][C:36]([NH:37][C:24]([C@@H:13]3[CH2:12][N:11]([C:9]([O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[O:10])[CH2:16][CH2:15][N:14]3[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:25])=[CH:35][CH:34]=2)=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 147633Benzenamine, 4-(4-fluorophenoxy)-HCID 70106521-(1,1-Dimethylethyl) 4-(phenylmethyl) (2S)-1,2,4-piperazinetricarboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 56954160(S)-4-benzyl 1-tert-butyl 2-(4-(4-fluorophenoxy)phenylcarbamoyl)piperazine-1,4-dicarboxylateYield 100.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Step (a) A flask was charged with (S)-4-(benzyloxycarbonyl)-1-(tert-butoxycarbonyl)piperazine-2-carboxylic acid (1 g, 2.74 mmol), obtained commercially, 4-(4-fluorophenoxy)aniline (558 mg, 2.75 mmol), DIEA (3 mL, 17.3 mmol), HATU (1.15 g, 3.03 mmol) and DMF (8 mL). The reaction mixture was stirred at ambient temperature for 20 minutes and then quenched with saturated sodium bicarbonate (aq., 10 mL). The mixture was extracted with ethyl acetate (20 mL) and the extract was washed with deionized water (10 mL) and then brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give (S)-4-benzyl 1-tert-butyl 2-(4-(4-fluorophenoxy)phenylcarbamoyl)piperazine-1,4-dicarboxylate (1.46 g, 2.75 mmol), which was carried forward without further purification.

Workup

  1. customobtained commercially
  2. customquenched with saturated sodium bicarbonate (aq., 10 mL)
  3. extractionThe mixture was extracted with ethyl acetate (20 mL)
  4. washthe extract was washed with deionized water (10 mL)
  5. dry with materialbrine (10 mL), dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-6584f05368124300a644410ab6ffd0ec
Source dataset
uspto-grants-2014_07
Patent number
US08791102B2

Reaction notes

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