Water → HCID 86591621, compound

HRID 1295719Notes

Reaction equation

HRID 1295719 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:15](=[O:20])[NH:16][CH:17]=[CH:18][N:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC([O-])(C)C.[K+].[F:27][C:28]1[CH:43]=[C:42]([F:44])[C:41]([F:45])=[CH:40][C:29]=1[O:30][CH2:31][CH2:32][CH2:33][CH2:34]OS(C)(=O)=O.O>C1COCC1>[F:27][C:28]1[CH:43]=[C:42]([F:44])[C:41]([F:45])=[CH:40][C:29]=1[O:30][CH2:31][CH2:32][CH2:33][CH2:34][N:16]1[CH:17]=[CH:18][N:19]=[C:14]([N:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][CH2:12]2)[C:15]1=[O:20]

Participants

6

Reactant 4

HCID 962WaterHCID 23665647Potassium tert-butoxideHCID 590138923-(4-tert-Butoxycarbonyl-1-piperazinyl)-2(1H)-pyrazinoneHCID 86591622HCID 86591622, compound

Product 1

HCID 86591621HCID 86591621, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of 3-(4-tert-butoxycarbonyl-1-piperazinyl)-2(1H)-pyrazinone (1.20 g, 4.30 mmol; from Example 48, Step 1) and t-BuOK (730 mg, 6.50 mmol) in THF (10 mL) was stirred for 10 min, and then added to a solution of methanesulfonic acid 4-(2,4,5-trifluoro-phenoxy)butyl ester (1.23 g, 4.3 nmol; from Step 2) in THF (50 mL). After being stirred at room temperature for 1 day, HPLC showed about 30% conversion. After 3 days, the reaction was worked up: water was added, THF was evaporated off and the aqueous mixture was extracted twice with EtOAc, dried and concentrated to yield 2.21 g of the crude product as a yellow oil. HPLC analysis showed a 5/1 ratio between the title product and the isomeric O-alkylated product.* Purification by chromatography on silica gel using EtOAc/hexane (1/2 to 1/1) as eluent gave 870 mg (42%) of the title product as a colorless oil. HPLC purity: 95%. MS m/z 483 (M+H)+. *Assignments were based on NMR analysis.

Workup

  1. stirringAfter being stirred at room temperature for 1 day
  2. waitAfter 3 days
  3. customTHF was evaporated off
  4. extractionthe aqueous mixture was extracted twice with EtOAc
  5. customdried
  6. concentrationconcentrated
  7. customto yield 2.21 g of the crude product as a yellow oil

Sources & evidence

ORD record
ord-616bf386457d4fe4aeea7a861108495e
Source dataset
uspto-grants-2007_07
Patent number
US07244722B2

Reaction notes

Loading…