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

HRID 1519457Notes

Reaction equation

HRID 1519457 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-0e877d48adb34dfa8dcf428d90b8b5b0
Source dataset
uspto-grants-2015_07
Patent number
US09073878B2

Reaction notes

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