1,8-Diazabicyclo(5.4.0)undec-7-ene → (R)-N-(5-bromo-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide

HRID 473116Notes

Reaction equation

HRID 473116 reaction equation
CC1(C)[C@@H]2CC[C@@]1(CS(O)(=O)=O)C(=O)C2.[Br:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[CH2:22][C@@H:21]([NH2:26])[CH2:20]2.C1CCN2C(=NCCC2)CC1.[CH3:38][CH:39]([S:41](Cl)(=[O:43])=[O:42])[CH3:40]>C(Cl)Cl.Cl>[Br:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[CH2:22][C@@H:21]([NH:26][S:41]([CH:39]([CH3:40])[CH3:38])(=[O:43])=[O:42])[CH2:20]2

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 824082-Propanesulfonyl chlorideHCID 46899975(R)-5-Bromo-2-aminoindan(1S)-(+)-10-camphorsulfonate

Product 1

HCID 46899976(R)-N-(5-bromo-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamideYield 87%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent2×

Procedure

(R)-5-bromo-2,3-dihydro-1H-inden-2-amine((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonate (7.88 mmol, 3.5 g) was suspended in DCM (40 mL) and DBU (23.63 mmol, 3.53 mL, 3.60 g) was added. The mixture was purged with nitrogen and cooled in an ice bath before dropwise addition of propane-2-sulfonyl chloride (15.75 mmol, 1.760 mL, 2.246 g). Stirring was continued at 0° C. for 1 h before allowing to come to room temperature. The mixture was diluted with DCM (100 mL) and 1N HCl (100 mL) and the phases mixed and separated. The aqueous phase was further extracted with DCM (2×100 mL) before combined organics were washed with brine. Concentration gave a light yellow oil which was purified on silica eluting with 75% DCM/heptane then neat DCM. Desired fractions were collected and concentrated to give (R)-N-(5-bromo-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide as a colourless oil (2.18 g, 87%). 1H NMR (400 MHz, CDCl3) δ 1.39 (d, 6H) 2.88 (m, 2H) 3.17 (sept, 1H) 3.28 (m, 2H) 4.27 (m, 2H) 7.08 (d, 1H) 7.30 (d, 1H) 7.35 (s, 1H)

Workup

  1. customThe mixture was purged with nitrogen
  2. customto come to room temperature
  3. additionthe phases mixed
  4. customseparated
  5. extractionThe aqueous phase was further extracted with DCM (2×100 mL)
  6. washbefore combined organics were washed with brine
  7. concentrationConcentration
  8. customgave a light yellow oil which
  9. customwas purified on silica eluting with 75% DCM/heptane
  10. customDesired fractions were collected
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-a0c35e627b4f404f8489b6c17f9bdbd6
Source dataset
uspto-grants-2014_01
Patent number
US08633237B2

Reaction notes

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