Selectfluor → 3'-Fluoro-6'-(3-chloro-benzyloxy)-3,4,5,6-tetrahydro-2h-[1,2']bipyrazinyl-4-carboxylic acid tert-butyl ester

HRID 2182143Notes

Reaction equation

HRID 2182143 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[N:18][CH:17]=[C:16]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=3)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[B-](F)(F)(F)[F:30].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19]([F:30])=[N:18][CH:17]=[C:16]([O:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=3)[N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 2724933SelectfluorHCID 69732798Tert-butyl 4-(6-((3-chlorobenzyl)oxy)pyrazin-2-yl)piperazine-1-carboxylate

Product 1

HCID 697307393'-Fluoro-6'-(3-chloro-benzyloxy)-3,4,5,6-tetrahydro-2h-[1,2']bipyrazinyl-4-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 6′-(3-chloro-benzyloxy)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester (1-1b) (600 mg, 1.49 mmol) in acetonitrile (12.4 ml) at 0° C. under a nitrogen atmosphere was treated with Selectfluor™ ([1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]-octane bis(tetrafluoroborate)]) (526 mg, 1.49 mmol). The resulting mixture was allowed to warm to room temperature and stirred for 16 h. The reaction mixture was partitioned between CH2Cl2 and water. The organic phase was washed twice with water, twice with saturated aqueous NaHCO3 solution and twice with brine, dried over MgSO4 (anhydrous), filtered and concentrated in vacuo. The residue was purified by flash chromatography (CHCl2-EtOAc 99:1 to 95:5). Three compounds were obtained in the following elution order: difluorinated material (160 mg, 25%), Intermediate I-3i (32 mg, 5%) and Intermediate I-3i′ (141 mg, 22%). The structures of the two monofluorinated products were assigned by nuclear Overhauser effect (nOe) experiments.

Workup

  1. customThe reaction mixture was partitioned between CH2Cl2 and water
  2. washThe organic phase was washed twice with water, twice with saturated aqueous NaHCO3 solution and twice with brine
  3. dry with materialdried over MgSO4 (anhydrous)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (CHCl2-EtOAc 99:1 to 95:5)
  7. customThree compounds were obtained in the following elution order

Sources & evidence

ORD record
ord-02062b1702d44c90b9fad1a0db43850d
Source dataset
uspto-grants-2005_05
Patent number
US06894050B2

Reaction notes

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