Isobutylamine → di-tert-butyl (2R)-2-((2-methylpropyl)carbamoyl)-1,4-piperazinedicarboxylate

HRID 1972599Notes

Reaction equation

HRID 1972599 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C@@H:9]1[C:21]([OH:23])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:48][CH:49]([CH3:52])[CH2:50][NH2:51].CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:48][CH:49]([CH3:52])[CH2:50][NH:51][C:21]([C@H:9]1[CH2:10][N:11]([C:14]([O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:15])[CH2:12][CH2:13][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])=[O:23]

Participants

6

Reactant 4

HCID 6558IsobutylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 26339502(2R)-1,4-bis((tert-butoxy)carbonyl)piperazine-2-carboxylic acid

Product 1

HCID 66582729di-tert-butyl (2R)-2-((2-methylpropyl)carbamoyl)-1,4-piperazinedicarboxylateYield 118.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 20 mL vial was charged with ((2R)-1,4-bis(tert-butoxycarbonyl)-2-piperazinecarboxylic acid (1.52 g, 4.60 mmol, ASW MedChem Inc., New Brunswick, N.J.), HATU (2.10 g, 5.52 mmol, ChemImpex International Inc., Wood Dale, Ill.), 2-methylpropan-1-amine (0.457 mL, 4.60 mmol, Sigma-Aldrich, St. Louis, Mo.), DIPEA (1.60 mL, 9.19 mmol) and DMF (8 mL). The mixture was stirred at room temperature for 2.5 h. and then partitioned between water (80 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc (50 mL). The combined organic extracts were washed with saturated aqueous NaHCO3 (100 mL), water (100 mL) then brine (100 mL). The organics were dried over sodium sulfate, filtered and concentrated in vacuo to afford di-tert-butyl (2R)-2-((2-methylpropyl)carbamoyl)-1,4-piperazinedicarboxylate (2.10 g) as a light brown foam.

Workup

  1. custompartitioned between water (80 mL) and EtOAc (50 mL)
  2. extractionThe aqueous phase was extracted with EtOAc (50 mL)
  3. washThe combined organic extracts were washed with saturated aqueous NaHCO3 (100 mL), water (100 mL)
  4. dry with materialThe organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e18ff7ee9b784bdd925f9c463efee20a
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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