tert-Butanol → Tert-butyl (2-bromo-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-7-yl)carbamate

HRID 874407Notes

Reaction equation

HRID 874407 reaction equation
[C:1]([OH:5])([CH3:4])([CH3:3])[CH3:2].[Br:6][C:7]1[N:8]=[C:9]2[CH2:14][CH:13](C(O)=O)[CH2:12][CH2:11][N:10]2[CH:18]=1.[N-:19]=[N+]=[N-].P([O-])([O:31][C:32]1C=CC=CC=1)(OC1C=CC=CC=1)=O>C(N(CC)CC)C>[Br:6][C:7]1[N:8]=[C:9]2[CH2:14][CH:13]([NH:19][C:32](=[O:31])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:12][CH2:11][N:10]2[CH:18]=1

Participants

5

Reactant 3

HCID 6386tert-ButanolHCID 21964642Diphenylphosphate azideHCID 903832892-Bromo-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-7-carboxylic acid

Product 1

HCID 90383235Tert-butyl (2-bromo-5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-7-yl)carbamate

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Molecular Sieves 4A (6 g) was added to a tert-butanol (45 ml) solution of the 2-bromo-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-7-carboxylic acid (3.1 g) obtained in (Example 2.7) <Step 3> and triethylamine (9.7 ml), and the obtained mixture was then stirred at room temperature for 30 minutes. Thereafter, diphenyl phosphate azide (3.8 ml) was added to the reaction solution, and the obtained mixture was stirred for 30 minutes and then at 110° C. for 4 hours. Thereafter, the reaction solution was filtered with Celite, and insoluble matters were then washed with ethyl acetate. After that, ethyl acetate (100 ml) was added to the filtrate, and the obtained mixture was successively washed with a saturated ammonium chloride aqueous solution (25 ml) three times, a saturated sodium hydrogen carbonate aqueous solution (25 ml) twice, and a saturated saline. Then, the solvent was distilled away under reduced pressure. Methylene chloride was added to the obtained residue, and precipitated white insoluble matters were then removed by suction filtration. The filtrate was concentrated under reduced pressure, and the obtained residue was then purified by silica gel column chromatography (silica gel: eluent; heptane:ethyl acetate=60:40-20:80), so as to obtain the title compound (1.3 g) in the form of a white solid.

Workup

  1. stirringthe obtained mixture was stirred for 30 minutes
  2. waitat 110° C. for 4 hours
  3. filtrationThereafter, the reaction solution was filtered with Celite, and insoluble matters
  4. washwere then washed with ethyl acetate
  5. additionAfter that, ethyl acetate (100 ml) was added to the filtrate
  6. washthe obtained mixture was successively washed with a saturated ammonium chloride aqueous solution (25 ml) three times
  7. distillationThen, the solvent was distilled away under reduced pressure
  8. additionMethylene chloride was added to the obtained residue
  9. customprecipitated white insoluble matters
  10. customwere then removed by suction filtration
  11. concentrationThe filtrate was concentrated under reduced pressure
  12. customthe obtained residue was then purified by silica gel column chromatography (silica gel: eluent; heptane:ethyl acetate=60:40-20:80)

Sources & evidence

ORD record
ord-cb27ea7dfbd249bbac4a0cc6e2ee42f5
Source dataset
uspto-grants-2015_03
Patent number
US08980889B2

Reaction notes

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