3-Pyridinemethanol → {1-[3-(Pyridin-4-ylmethoxy)-pyrazin-2-yl]-pyrrolidin-3-yl}-carbamic acid tert-butyl ester

HRID 907562Notes

Reaction equation

HRID 907562 reaction equation
C[C:2](C)([O-:4])C.[K+].[CH:7]1[CH:12]=[N:11][CH:10]=[C:9](CO)[CH:8]=1.[C:15]([O:19][C:20](=[O:34])[NH:21][CH:22]1[CH2:26][CH2:25][N:24]([C:27]2[C:32](Cl)=[N:31][CH:30]=[CH:29][N:28]=2)[CH2:23]1)([CH3:18])([CH3:17])[CH3:16]>C(O)(C)(C)C>[C:15]([O:19][C:20](=[O:34])[NH:21][CH:22]1[CH2:26][CH2:25][N:24]([C:27]2[C:32]([O:4][CH2:2][C:8]3[CH:7]=[CH:12][N:11]=[CH:10][CH:9]=3)=[N:31][CH:30]=[CH:29][N:28]=2)[CH2:23]1)([CH3:18])([CH3:17])[CH3:16]

Participants

5

Reactant 3

HCID 75103-PyridinemethanolHCID 23665647Potassium tert-butoxideHCID 59013776Tert-butyl (1-(3-chloropyrazin-2-yl)pyrrolidin-3-yl)carbamate

Product 1

HCID 59013922{1-[3-(Pyridin-4-ylmethoxy)-pyrazin-2-yl]-pyrrolidin-3-yl}-carbamic acid tert-butyl esterYield 12%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Procedure

To a round-bottom flask purged with N2 was charged with Potassium t-butoxide (7.6 g, 68.4 mmol) and t-butanol (140 mL). The mixture was flushed with N2 for approximately 5 min., while stirring. To this mixture was added pyridylcarbinol (7.4 g, 68.4 mmol), followed by [1-(3-chloro-pyrazin-2-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (6.8 g, 22.8 mmol). The mixture was stirred at room temperature overnight. The mixture was concentrated in vacuo, and then diluted with water and extracted with EtOAc three times. The organic layer was washed with water and brine, dried over sodium sulfate, and then concentrated in vacuo. Purification of the crude by column chromatography afforded {1-[3-(pyridin-4-ylmethoxy)-pyrazin-2-yl]-pyrrolidin-3-yl}-carbamic acid tert-butyl ester (1 g, 12% yield).

Workup

  1. customTo a round-bottom flask purged with N2
  2. customThe mixture was flushed with N2 for approximately 5 min.
  3. stirringThe mixture was stirred at room temperature overnight
  4. concentrationThe mixture was concentrated in vacuo
  5. additiondiluted with water
  6. extractionextracted with EtOAc three times
  7. washThe organic layer was washed with water and brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customPurification of the crude by column chromatography

Sources & evidence

ORD record
ord-7aa25689392242e8b40eb4a90e460fd8
Source dataset
uspto-grants-2011_09
Patent number
US08013156B2

Reaction notes

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