Sodium hydride → HCID 86761570, compound

HRID 1926658Notes

Reaction equation

HRID 1926658 reaction equation
[OH:1][C:2]1([C:13]([F:16])([F:15])[F:14])[CH2:5][N:4]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:3]1.[Cl:17][C:18]1[CH:23]=[N:22][CH:21]=[C:20](Cl)[N:19]=1.[H-].[Na+]>CN(C=O)C>[Cl:17][C:18]1[N:19]=[C:20]([O:1][C:2]2([C:13]([F:16])([F:14])[F:15])[CH2:3][N:4]([C:6]([O:8][C:9]([CH3:11])([CH3:12])[CH3:10])=[O:7])[CH2:5]2)[CH:21]=[N:22][CH:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 785042,6-DichloropyrazineHCID 50986409tert-butyl 3-hydroxy-3-(trifluoroMethyl)azetidine-1-carboxylate

Product 1

HCID 86761570HCID 86761570, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of tert-butyl 3-hydroxy-3-(trifluoromethyl)azetidine-1-carboxylate (0.37 g, 1.5 mmol) and 2,6-dichloropyrazine (0.23 g, 1.5 mmol) in DMF (5 mL) at 0° C. was added sodium hydride (60% mineral oil dispersion; 0.073 g, 1.8 mmol). The reaction mixture was allowed to warm to room temperature. After 15 minutes, the reaction mixture was partitioned between EtOAc (50 mL) and brine (50 mL). The organic layer was washed with additional brine (50 mL). The first aqueous layer was back-extracted with EtOAc (50 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (EtOAc/Hexanes gradient) to afford tert-butyl 3-[(6-chloropyrazine-2-yl)oxy]-3-(trifluoromethyl)azetidine-1-carboxylate. LRMS calculated for C13H15ClF3N3O3[M+H]+, 354.1; found 298.0 [M-tButyl+H]+. 1H NMR (600 MHz, DMSO-D6) 8.50 (s, 1H); 8.46 (s, 1H); 4.53 (br s, 2H); 4.20 (br d, 2H); 1.37 (s, 9H).

Workup

  1. customthe reaction mixture was partitioned between EtOAc (50 mL) and brine (50 mL)
  2. washThe organic layer was washed with additional brine (50 mL)
  3. extractionThe first aqueous layer was back-extracted with EtOAc (50 mL)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude residue was purified by silica gel chromatography (EtOAc/Hexanes gradient)

Sources & evidence

ORD record
ord-9687c594af8849658f463e0b2f88c179
Source dataset
uspto-grants-2012_05
Patent number
US08183245B2

Reaction notes

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