Potassium Carbonate → tert-butyl 6-bromopyridin-2-yl((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)carbamate

HRID 1963816Notes

Reaction equation

HRID 1963816 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].CC1C=CC(S(O[CH2:33][CH:34]2[CH2:39][CH2:38][O:37][C:36]([CH3:41])([CH3:40])[CH2:35]2)(=O)=O)=CC=1.[H-].[Na+]>CN(C=O)C.CCOC(C)=O.C([O-])(O)=O.[Na+]>[Br:1][C:2]1[N:7]=[C:6]([N:8]([CH2:33][CH:34]2[CH2:39][CH2:38][O:37][C:36]([CH3:41])([CH3:40])[CH2:35]2)[C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 13040380Tert-butyl (6-bromopyridin-2-YL)carbamateHCID 86653907(2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 58284736tert-butyl 6-bromopyridin-2-yl((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)carbamate

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
45 °C

Procedure

To a mixture of tert-butyl 6-bromopyridin-2-ylcarbamate (686 mg, 2.51 mmol), K2CO3 (347 mg, 2.51 mmol), (2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl 4-methylbenzenesulfonate (750 mg, 2.51 mmol) in DMF (10 mL) was added carefully NaH (60 wt. %, 141 mg, 3.52 mmol) in portions [Caution: gas development!]. The resulting mixture was stirred at about 45° C. for 4 hr. The mixture was warmed to ambient temperature and was diluted with EtOAc (˜50 mL) and saturated aqueous NaHCO3. The organic layer was separated, washed with saturated aqueous NaHCO3 solution (1×), dried over Na2SO4, filtered off and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 40 g, 25 min, EtOAc/heptane=0/100 to 25/75 over 25 min] providing (R/S)-tert-butyl 6-bromopyridin-2-yl((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)carbamate as highly viscous, colorless oil. Yield: 723 mg. LCMS (m/z): 344.9 {loss of tert Bu-group}/(399.0)[M+H]+; Retention time=1.22 min.

Workup

  1. temperatureThe mixture was warmed to ambient temperature
  2. customThe organic layer was separated
  3. washwashed with saturated aqueous NaHCO3 solution (1×)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered off
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by column chromatography [SiO2, 40 g, 25 min, EtOAc/heptane=0/100 to 25/75 over 25 min]

Sources & evidence

ORD record
ord-e671870217d44755938c6c8f5ca9e902
Source dataset
uspto-grants-2013_04
Patent number
US08415381B2

Reaction notes

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