Hydrogen Bromide → (R)-tert-butyl 2-(4-(pyridin-4-yl)thiazol-2-yl)pyrrolidine-1-carboxylate

HRID 1752292Notes

Reaction equation

HRID 1752292 reaction equation
[C:1]([C@H:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])(=[S:3])[NH2:2].Br[CH2:17][C:18]([C:20]1[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=1)=O.Br.C([O-])([O-])=O.[K+].[K+]>CCO>[N:23]1[CH:24]=[CH:25][C:20]([C:18]2[N:2]=[C:1]([C@H:4]3[CH2:8][CH2:7][CH2:6][N:5]3[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[S:3][CH:17]=2)=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 11430Potassium CarbonateHCID 4070312-Bromo-1-(pyridin-4-yl)ethanoneHCID 14019689tert-butyl (2R)-2-carbamothioylpyrrolidine-1-carboxylate

Product 1

HCID 67480237(R)-tert-butyl 2-(4-(pyridin-4-yl)thiazol-2-yl)pyrrolidine-1-carboxylateYield 37%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A stirred mixture of (R)-tert-butyl 2-carbamothioylpyrrolidine-1-carboxylate (373 mg, 1.6 mmol), 4-(bromoacetyl)pyridine.HBr (455 mg, 1.6 mmol), K2CO3 (224 mg, 1.6 mmol) and EtOH (20 mL) was heated at reflux for 4 h. The mixture was cooled and concentrated. The residues was taken up in EtOAc (90 mL), washed with 0.5 M aq NaoH (20 mL) and brine (20 mL), and dried over Na2SO4. Removal of the solvent left an amber oil (410 mg). A 379-mg portion of the crude product was purified by chromatography on a 12-g silica gel cartridge, eluted with a 0-100% EtOAc in hexanes gradient to afford (R)-tert-butyl 2-(4-(pyridin-4-yl)thiazol-2-yl)pyrrolidine-1-carboxylate (200 mg, 37%) as a tan solid. LC-MS Method 1 tR=1.20 min, m/z=332.

Workup

  1. temperatureat reflux for 4 h
  2. temperatureThe mixture was cooled
  3. concentrationconcentrated
  4. washwashed with 0.5 M aq NaoH (20 mL) and brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. customRemoval of the solvent
  7. waitleft an amber oil (410 mg)
  8. customA 379-mg portion of the crude product was purified by chromatography on a 12-g silica gel cartridge
  9. washeluted with a 0-100% EtOAc in hexanes gradient

Sources & evidence

ORD record
ord-7f58ff2826e541b9926743bf67d09867
Source dataset
uspto-grants-2015_10
Patent number
US09163012B2

Reaction notes

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