1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 86627324, compound

HRID 549447Notes

Reaction equation

HRID 549447 reaction equation
O[CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[CH2:4][C:3]1([CH3:14])[CH3:13].C1C=CC(P([N:29]=[N+:30]=[N-:31])(C2C=CC=CC=2)=O)=CC=1.C1CCN2C(=NCCC2)CC1>C1(C)C=CC=CC=1>[N:29]([CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[CH2:4][C:3]1([CH3:14])[CH3:13])=[N+:30]=[N-:31]

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 67081826HCID 67081826, compound2×

Product 1

HCID 86627324HCID 86627324, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of Step B. 3-hydroxy-2,2-dimethyl-2,3-dihydro-1H-indene-5-carbonitrile (4.98 g, 0.027 mol) in toluene (60 mL) at 0° C. was added DPPA (8.6 mL, 0.040 mol) via syringe dropwise followed by DBU (6.0 mL, 0.040 mol) via syringe dropwise. After stirring at 0° C. for 10 min and rt for 30 min, the mixture was heated at 80° C. for 60 h, then cooled to rt and partitioned between EtOAc (400 mL)/water (100 mL). Resulting layers were separated and the organic layer was washed with water (100 mL), aq HCl (1N, 60 mL×2), water (100 mL), sat. aq. NaHCO3 (80 mL), brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give yellow oil as the crude product. Purification by flash chromatography on silica gel (120 g) eluting with EtOAc/hexane mixtures provided the title compound as a colorless oil (4.12 g, 73% yield). HPLC Ret. time: 3.37 min. LCMS MH+ (m/z) 213.3. 1H NMR: (DMSO-d6, 400 MHz): δ 7.86 (s, 1H), 7.76 (d, 1H), 7.49 (d, 1H), 4.74 (s, 1H), 2.80 (m, 2H), 1.13 (s, 3H), 1.06 (s, 3H).

Workup

  1. temperaturethe mixture was heated at 80° C. for 60 h
  2. temperaturecooled to rt
  3. custompartitioned between EtOAc (400 mL)/water (100 mL)
  4. customResulting layers were separated
  5. washthe organic layer was washed with water (100 mL), aq HCl (1N, 60 mL×2), water (100 mL), sat. aq. NaHCO3 (80 mL), brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give yellow oil as the crude product
  10. customPurification by flash chromatography on silica gel (120 g)
  11. washeluting with EtOAc/hexane

Sources & evidence

ORD record
ord-b980323b02a74737be91306143263f60
Source dataset
uspto-grants-2011_05
Patent number
US07943658B2

Reaction notes

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