Dimethyl Sulfoxide → 4-{3-Oxo-4-[2-(2,4,5-trifluoro-phenoxy)-ethyl]-3,4-dihydro-quinoxalin-2-yl}-piperazine-1-carboxylic acid tert-butyl ester

HRID 1295705Notes

Reaction equation

HRID 1295705 reaction equation
CC([O-])(C)C.[K+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][N:17]([C:20]2[C:29](=[O:30])[NH:28][C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].CS(C)=O.CS(O[CH2:40][CH2:41][O:42][C:43]1[CH:48]=[C:47]([F:49])[C:46]([F:50])=[CH:45][C:44]=1[F:51])(=O)=O>C1COCC1.CCOC(C)=O.O>[C:7]([O:11][C:12]([N:14]1[CH2:15][CH2:16][N:17]([C:20]2[C:29](=[O:30])[N:28]([CH2:40][CH2:41][O:42][C:43]3[CH:48]=[C:47]([F:49])[C:46]([F:50])=[CH:45][C:44]=3[F:51])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=2)[CH2:18][CH2:19]1)=[O:13])([CH3:10])([CH3:8])[CH3:9]

Participants

8

Reactant 4

HCID 679Dimethyl SulfoxideHCID 23665647Potassium tert-butoxideHCID 693660094-(3-Oxo-3,4-dihydro-quinoxalin-2-yl)-piperazine-1-carboxylic acid tert-butyl esterHCID 865916192-(2,4,5-Trifluorophenoxy)ethyl methanesulfonate

Product 1

HCID 693662774-{3-Oxo-4-[2-(2,4,5-trifluoro-phenoxy)-ethyl]-3,4-dihydro-quinoxalin-2-yl}-piperazine-1-carboxylic acid tert-butyl esterYield 11%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

t-BuOK (1.0 g, 8.9 mmol) was added to a mixture of 4-(3-oxo-3,4-dihydro-quinoxalin-2-yl)-piperazine-1-carboxylic acid tert-butyl ester (1 g, 9 mmol; from Step 2), THF (20 g) and DMSO (5 g) at room temperature. This mixture is added to a solution of 2-(2,4,5-trifluorophenoxy)ethyl methanesulfonate (2.45 g, 9.00 mmol; from Example 54, Step 4) in THF (20 g). After being stirred at room temperature overnight, water (100 g) and EtOAc (200 g) were added to the reaction mixture. The layers were separated and the organic layer was concentrated in vacuo. The residue was purified by chromatography on an MPLC-columnn using a continuous gradient (0-100% EtOAc in heptane) as eluent. Evaporation of solvent gave 0.5 g of the title compound as greasy crystals (not pure). 1H NMR analysis supports the stated structure. This material was used directly in the next step.

Workup

  1. customThe layers were separated
  2. concentrationthe organic layer was concentrated in vacuo
  3. customThe residue was purified by chromatography on an MPLC-columnn
  4. customEvaporation of solvent

Sources & evidence

ORD record
ord-bfebd1087dbc486991c6db10622a97c7
Source dataset
uspto-grants-2007_07
Patent number
US07244722B2

Reaction notes

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