Methylglyoxal → HCID 15407404, compound

HRID 1979087Notes

Reaction equation

HRID 1979087 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:15](=O)[C:16]([CH3:18])=[O:17].C1(C)C(S([CH:29]([N+:37]#[C-:38])[C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)(=O)=O)=CC=CC=1.C([O-])([O-])=O.[K+].[K+]>CCOCC.CCOC(C)=O.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:15]([C:16](=[O:17])[CH3:18])=[C:29]([C:30]3[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=3)[N:37]=[CH:38]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 880MethylglyoxalHCID 11430Potassium CarbonateHCID 12682914-Amino-1-Boc-piperidineHCID 11140792HCID 11140792, compound

Product 1

HCID 15407404HCID 15407404, compoundYield 27.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of t-butyl-4-amino-piperidinecarboxylate (0.95 g, 4.75 mmol) in 40 mL of Et2O was added pyruvaldehyde (40% w/w solution in water, 0.94 mL, 1.11 g, 6.17 mmol) at room temperature. After 1.75 h, the solution was poured into a separatory funnel, diluted with 30 mL of Et2O and 10 mL of EtOAc, and washed with 2×10 mL of water. The organics were concentrated in vacuo and the residue was diluted in 10 mL of DMF and α-(toluenesulfonyl)-4-fluoro-benzylisonitrile (1.37 g, 4.75 mmol) and K2CO3 (0.72 g, 5.23 mmol) were added. After 16 h, the solution was diluted with 100 mL of water and extracted with 2×40 mL of EtOAc. The combined organics were washed with 3×40 mL of 10% HCl. The aqueous layers were combined and neutralized with excess solid NaHCO3, then basified with 20 mL of 10% KOH. The aqueous layer was transferred to a separatory funnel and extracted 3×30 mL of EtOAc. The combined organics concentrated in vacuo to yield the imidazole product (0.5 g, 27%): 1H NMR (CDCl3) δ 7.74, 7.44 (2H, m), 7.13 (2H, t, J=8.6 Hz), 4.97 (1H, tt, J=3.7, 12.0 Hz), 4.29 (2H, m), 2.88 (2H, m), 2.15 (2H, m), 2.11 (3H, s), 1.78 (2H, dq, 4.2, 12.2 Hz), 1.48 (9H, s).

Workup

  1. additionthe solution was poured into a separatory funnel
  2. washwashed with 2×10 mL of water
  3. concentrationThe organics were concentrated in vacuo
  4. additionthe residue was diluted in 10 mL of DMF
  5. waitAfter 16 h
  6. extractionextracted with 2×40 mL of EtOAc
  7. washThe combined organics were washed with 3×40 mL of 10% HCl
  8. customThe aqueous layer was transferred to a separatory funnel
  9. extractionextracted 3×30 mL of EtOAc
  10. concentrationThe combined organics concentrated in vacuo

Sources & evidence

ORD record
ord-c71fc61e322a476a968f309ad222492b
Source dataset
uspto-grants-2001_05
Patent number
US06239279B1

Reaction notes

Loading…