Water → Methyl 4-((R)-1-(4-(((R)-1-(3,4-dichlorobenzenesulfonyl)-3-oxo-1,2,3,4-tetrahydro-pyrazin-2-yl)methyl)-1H-1,2,3-triazol-1-yl)ethyl)benzoate

HRID 1432020Notes

Reaction equation

HRID 1432020 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([N:12]2[CH:17]=[CH:16][NH:15][C:14](=[O:18])[C@H:13]2[CH2:19][C:20]#[CH:21])(=[O:11])=[O:10])[CH:5]=[CH:6][C:7]=1[Cl:8].[N:22]([C@@H:25]([C:27]1[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=1)[CH3:26])=[N+:23]=[N-:24].[Na].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.O>O1CCOCC1.C(O)(C)(C)C>[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([N:12]2[CH:17]=[CH:16][NH:15][C:14](=[O:18])[C@H:13]2[CH2:19][C:20]2[N:24]=[N:23][N:22]([C@@H:25]([C:27]3[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=3)[CH3:26])[CH:21]=2)(=[O:11])=[O:10])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

7

Reactant 4

HCID 962WaterHCID 16108955Methyl 4-[(1R)-1-azidoethyl]benzoateHCID 86604867(R)-4-(3,4-dichlorobenzenesulfonyl)-3-(prop-2-ynyl)-3,4-dihydropyrazin-2(1H)-oneHCID 178519209sodium (L)-ascorbate

Product 1

HCID 57932491Methyl 4-((R)-1-(4-(((R)-1-(3,4-dichlorobenzenesulfonyl)-3-oxo-1,2,3,4-tetrahydro-pyrazin-2-yl)methyl)-1H-1,2,3-triazol-1-yl)ethyl)benzoate

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (R)-4-(3,4-dichlorobenzenesulfonyl)-3-(prop-2-ynyl)-3,4-dihydro-pyrazin-2(1H)-one (1.46 g, 4.24 mmol) and (R)-methyl 4-(1-azidoethyl)benzoate (0.870 g, 4.24 mmol) in dioxane (80 mL) and tert-butanol (120 mL) were added CuSO4.5H2O (1.11 g, 4.46 mmol in 8.0 mL H2O) and sodium-L-ascorbate (0.880 g, 4.44 mmol in 8.0 mL H2O). After 5 min, H2O (40 mL) was added and the reaction mixture was stirred for 16 h. The solvent was concentrated to approximately 40 mL under reduced pressure and diluted with 200 mL EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc (1×100 mL). The extracts were washed with 5% NaHCO3 (200 mL×2), brine (200 mL×2), dried over Na2SO4 and concentrated under reduced pressure. The crude product was chromatographed on silica (100% CH2Cl2 to 10% MeOH in CH2Cl2) to yield the title compound.

Workup

  1. concentrationThe solvent was concentrated to approximately 40 mL under reduced pressure
  2. additiondiluted with 200 mL EtOAc
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (1×100 mL)
  5. washThe extracts were washed with 5% NaHCO3 (200 mL×2), brine (200 mL×2)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was chromatographed on silica (100% CH2Cl2 to 10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-df44dd01047548f687ca0d9be56e9c18
Source dataset
uspto-grants-2009_11
Patent number
US07612060B2

Reaction notes

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