Oxalyl chloride → Methyl 2-[1-(2-methyl-4-quinolyl)-4-[(E)-4,4,4-trifluorobut-2-enoyl]piperazin-2-yl]acetate

HRID 333983Notes

Reaction equation

HRID 333983 reaction equation
[F:1][C:2]([F:9])([F:8])/[CH:3]=[CH:4]/[C:5](O)=[O:6].C(Cl)(=O)C(Cl)=O.[CH3:16][C:17]1[CH:26]=[C:25]([N:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH:28]2[CH2:33][C:34]([O:36][CH3:37])=[O:35])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl.CN(C=O)C>[CH3:16][C:17]1[CH:26]=[C:25]([N:27]2[CH2:32][CH2:31][N:30]([C:5](=[O:6])/[CH:4]=[CH:3]/[C:2]([F:9])([F:8])[F:1])[CH2:29][CH:28]2[CH2:33][C:34]([O:36][CH3:37])=[O:35])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]=1

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 57096144,4,4-Trifluorocrotonic acidHCID 66835808Methyl 2-[1-(2-methyl-4-quinolyl)piperazin-2-yl]acetate

Product 1

HCID 66836038Methyl 2-[1-(2-methyl-4-quinolyl)-4-[(E)-4,4,4-trifluorobut-2-enoyl]piperazin-2-yl]acetate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

(E)-4,4,4-Trifluorobut-2-enoic acid (15.4 mg, 0.08 mmol) was dissolved in DCM (1 ml), oxalyl chloride was added (9.4 μl, 0.11 mmol) followed by a drop of DMF. The mixture was stirred for 10 minutes at room temperature. Methyl 2-[1-(2-methyl-4-quinolyl)piperazin-2-yl]acetate (33.6 mg, 0.1 mmol) was dissolved in DMF (1 ml) together with diisopropylethylamine (44 μl, 0.25 mmol), the solutions were combined and the resulting mixture was stirred at room temperature overnight. The volatiles were removed under reduced pressure and the residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 3.9 mg (0.0093 mmol, 9%).

Workup

  1. stirringthe resulting mixture was stirred at room temperature overnight
  2. customThe volatiles were removed under reduced pressure
  3. customthe residue was purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile)
  4. customto yield 3.9 mg (0.0093 mmol, 9%)

Sources & evidence

ORD record
ord-dd90ecebe18949c88a1ffafc59729ca2
Source dataset
uspto-grants-2014_11
Patent number
US08883791B2

Reaction notes

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