Isopropylamine → di-tert-butyl (2R)-2-((1-methylethyl)carbamoyl)-1,4-piperazinedicarboxylate

HRID 1972607Notes

Reaction equation

HRID 1972607 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](O)=[O:22])=[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]([NH2:51])[CH3:50].CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:48][CH:49]([NH:51][C:21]([C@H:9]1[CH2:10][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:18])[CH3:19])=[O:15])[CH2:12][CH2:13][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[O:22])[CH3:50]

Participants

6

Reactant 4

HCID 6363IsopropylamineHCID 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 66583022di-tert-butyl (2R)-2-((1-methylethyl)carbamoyl)-1,4-piperazinedicarboxylateYield 130.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 20-mL vial was charged with ((2R)-1,4-bis(tert-butoxycarbonyl)-2-piperazinecarboxylic acid (1.57 g, 4.76 mmol, ASW MedChem Inc., New Brunswick, N.J.), HATU (2.17 g, 5.72 mmol, ChemImpex International Inc., Wood Dale, Ill.), propan-2-amine (0.450 mL, 5.28 mmol, Sigma-Aldrich, St. Louis, Mo.), DIPEA (1.70 mL, 9.76 mmol) and DMF (8 mL). The mixture was stirred at room temperature for 2.5 h. The reaction mixture was partitioned between water (80 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc (50 mL). and the combined organic phases were washed with saturated aqueous NaHCO3 (100 mL), water (100 mL), then brine (100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford di-tert-butyl (2R)-2-((1-methylethyl)carbamoyl)-1,4-piperazinedicarboxylate (2.30 g) as a light-brown foam.

Workup

  1. customThe reaction mixture was partitioned between water (80 mL) and EtOAc (50 mL)
  2. extractionThe aqueous phase was extracted with EtOAc (50 mL)
  3. washand the combined organic phases were washed with saturated aqueous NaHCO3 (100 mL), water (100 mL)
  4. dry with materialbrine (100 mL), dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0694084150db46259116c5722c84da70
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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