Cesium carbonate → 2-Chloro-6-(4,4-difluoropiperidin-1-yl)pyrazine

HRID 634093Notes

Reaction equation

HRID 634093 reaction equation
Cl.[F:2][C:3]1([F:9])[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.C([O-])([O-])=O.[Cs+].[Cs+].[Cl:16][C:17]1[CH:22]=[N:21][CH:20]=[C:19](Cl)[N:18]=1>CN(C=O)C.CCOC(C)=O>[Cl:16][C:17]1[CH:22]=[N:21][CH:20]=[C:19]([N:6]2[CH2:7][CH2:8][C:3]([F:9])([F:2])[CH2:4][CH2:5]2)[N:18]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 785042,6-DichloropyrazineHCID 27583514,4-Difluoropiperidine hydrochloride

Product 1

HCID 867250902-Chloro-6-(4,4-difluoropiperidin-1-yl)pyrazineYield 85%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4,4-difluoropiperidine hydrochloride (598 mg, 3.79 mmol), Cs2CO3 (2471 mg, 7.58 mmol) and 2,6-dichloropyrazine (538 mg, 3.61 mmol) in DMF (5 mL) was heated in a microwave at 100° C. for 35 min. The mixture was diluted with EtOAc (50 mL) and washed with 2×5 mL of H2O. The organic layer was dried, filtered and concentrated. The residue was purified on a silica gel column (eluting with 25-35% EtOAc in Hex) to give 2-chloro-6-(4,4-difluoropiperidin-1-yl)pyrazine (717 mg, 85%) as a brown amorphous solid. MS (ESI, pos. ion) m/z 234.1 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 8.39 (s, 1H), 7.89 (s, 1H), 3.75 (t, J=5.7 Hz, 4H), 2.06 (m, 4H).

Workup

  1. washwashed with 2×5 mL of H2O
  2. customThe organic layer was dried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified on a silica gel column (eluting with 25-35% EtOAc in Hex)

Sources & evidence

ORD record
ord-15769949a2e94bf0aa1fb7ead2a292eb
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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