Diisopropylethylamine → di-tert-butyl (2R)-2-(((3S)-3-methyl-4-morpholinyl)carbonyl)-1,4-piperazinedicarboxylate

HRID 1972588Notes

Reaction equation

HRID 1972588 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].[CH3:24][C@H:25]1[CH2:30][O:29][CH2:28][CH2:27][NH:26]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:24][C@H:25]1[CH2:30][O:29][CH2:28][CH2:27][N:26]1[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]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)2×HCID 12012220(3S)-3-methylmorpholineHCID 26339502(2R)-1,4-bis((tert-butoxy)carbonyl)piperazine-2-carboxylic acid

Product 1

HCID 66582920di-tert-butyl (2R)-2-(((3S)-3-methyl-4-morpholinyl)carbonyl)-1,4-piperazinedicarboxylateYield 106.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 100-mL round-bottomed flask was charged with (R)-1,4-bis(tert-butoxycarbonyl)piperazine-2-carboxylic acid (2.04 g, 6.17 mmol, ASW MedChem. Inc., New Brunswick, N.J.), (S)-3-methylmorpholine (0.657 g, 6.50 mmol, Synthetech Inc., Albany, Oreg.), HATU (2.83 g, 7.45 mmol, ChemImpex International Inc., Wood Dale, Ill.), DIPEA (2.20 mL, 12.6 mmol) and DMF (12 mL). The reaction mixture was stirred at room temperature for 1 h. After this time, additional HATU (0.475 g) was added and the stirring at room temperature was resumed for 2 days. The reaction mixture was partitioned between water (120 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc (2×40 mL). The combined organic phases were washed with water (50 mL), saturated aqueous NaHCO3 (50 mL), water (50 mL) and saturated aqueous NaCl (50 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford di-tert-butyl (2R)-2-(((3S)-3-methyl-4-morpholinyl)carbonyl)-1,4-piperazinedicarboxylate (2.71 g) as a light-brown solid.

Workup

  1. waitthe stirring at room temperature was resumed for 2 days
  2. customThe reaction mixture was partitioned between water (120 mL) and EtOAc (50 mL)
  3. extractionThe aqueous phase was extracted with EtOAc (2×40 mL)
  4. washThe combined organic phases were washed with water (50 mL), saturated aqueous NaHCO3 (50 mL), water (50 mL) and saturated aqueous NaCl (50 mL)
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-65342f0f199943aa867c1586db89fb9a
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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