Cesium carbonate → [3-(5-Bromo-2-chloro-pyrimidin-4-yloxy)-cyclobutyl]-carbamic acid tert-butyl ester

HRID 1846824Notes

Reaction equation

HRID 1846824 reaction equation
[C:1]([O:5][C:6](=[O:13])[NH:7][CH:8]1[CH2:11][CH:10]([OH:12])[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].[Br:20][C:21]1[C:22](Cl)=[N:23][C:24]([Cl:27])=[N:25][CH:26]=1>C1COCC1>[C:1]([O:5][C:6](=[O:13])[NH:7][CH:8]1[CH2:11][CH:10]([O:12][C:22]2[C:21]([Br:20])=[CH:26][N:25]=[C:24]([Cl:27])[N:23]=2)[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 2899735-Bromo-2,4-dichloropyrimidineHCID 22594430tert-Butyl (3-hydroxycyclobutyl)carbamate

Product 1

HCID 58548640[3-(5-Bromo-2-chloro-pyrimidin-4-yloxy)-cyclobutyl]-carbamic acid tert-butyl esterYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3-hydroxy-cyclobutyl)-carbamic acid tert-butyl ester (2.5 g, 13.3 mmol) in THF (40 mL) were added Cs2CO3 (8.6 g, 26.6 mmol) and 5-bromo-2,4-dichloro-pyrimidine (3 g, 13.3 mmol). The reaction mixture was heated at reflux overnight. The reaction mixture was filtered and concentrated, diluted with EtOAc and water. The aqueous phase was extracted with EtOAc (3×100 mL) and the combined organic extracts were washed with brine (60 mL), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel to give the product (4.75 g, 12.6 mmol, yield: 95%). ESI-MS (M+1): 378 calc. for C13H17BrClN3O3 377.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. filtrationThe reaction mixture was filtered
  4. concentrationconcentrated
  5. additiondiluted with EtOAc and water
  6. extractionThe aqueous phase was extracted with EtOAc (3×100 mL)
  7. washthe combined organic extracts were washed with brine (60 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-a83f18f38fec4b1aad37f75dce3412a0
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

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