Isopropyl isocyanate → Benzyl 4-(Isopropylcarbamoyl)piperazine-1-carboxylate

HRID 922404Notes

Reaction equation

HRID 922404 reaction equation
[N:1]1([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C(N(C(C)C)CC)(C)C.[N:26]([CH:29]([CH3:31])[CH3:30])=[C:27]=[O:28]>ClCCl.CCOC(C)=O>[CH:29]([NH:26][C:27]([N:4]1[CH2:5][CH2:6][N:1]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:2][CH2:3]1)=[O:28])([CH3:31])[CH3:30]

Participants

6

Reactant 3

HCID 61277Isopropyl isocyanateHCID 81531DiisopropylethylamineHCID 643495Benzyl piperazine-1-carboxylate

Product 1

HCID 86719361Benzyl 4-(Isopropylcarbamoyl)piperazine-1-carboxylateYield 57%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of benzyl piperazine-1-carboxylate (1, 5.0 g, 23 mmol) and diisopropylethylamine (5.86 g, 45.4 mmol) in dichloromethane (50 mL) was added 2-isocyanatopropane (4.83 g, 56.8 mmol) and the mixture was stirred overnight at room temperature. The mixture was diluted with EtOAc (300 mL), washed with water (100 mL), dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel chromatography eluting with to 0-20% CH2Cl2/92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2 to afford the title compound (3.94 g, 57%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.45-7.25 (m, 5H), 5.14 (s, 2H), 4.19 (d, J=6.7 Hz, 1H), 4.05-3.90 (m, 1H), 3.60-3.45 (m, 4H), 3.44-3.25 (m, 4H), 1.20-1.10 (m, 6H); Multimode MS m/z 306 [M+H]+.

Workup

  1. washwashed with water (100 mL)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with to 0-20% CH2Cl2/92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2

Sources & evidence

ORD record
ord-8fe2c01fb4154890bba4948ccf09f491
Source dataset
uspto-grants-2016_03
Patent number
US09278940B2

Reaction notes

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