Allyl bromide → HCID 19753237, compound

HRID 1647040Notes

Reaction equation

HRID 1647040 reaction equation
[H-].[Na+].[C:3]([NH:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[CH2:19][CH2:18][CH2:17]2)([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].[H][H].[CH2:25](Br)[CH:26]=[CH2:27]>C(OCC)(=O)C.O.O1CCCC1>[C:3]([N:13]([CH2:27][CH:26]=[CH2:25])[C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[CH2:19][CH2:18][CH2:17]2)([O:5][CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)=[O:4]

Participants

8

Reactant 4

HCID 7841Allyl bromideHCID 24758Sodium hydrideHCID 19753252HCID 19753252, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 19753237HCID 19753237, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A sodium hydride/mineral oil dispersion (50%, 2.00 g) is carefully added to a solution of N-(carbobenzyloxy)-5-aminoindan (XVIA, EXAMPLE 41, 8.856 g) in freshly distilled tetrahydrofuran (about 350 ml) at 20° under argon. The reaction is mildly exothermic with evolution of hydrogen gas. Allyl bromide (3.4 ml, 4.8 g) is then added over 1 min. The mixture is stirred at 20°-25° for 1 hr forming a solid. The mixture is then heated at reflux for 3.5 hr then stirred at 20°-25° overnight. An aliquot is taken, poured into water and ethyl acetate, and the organic layer evaporated. NMR analysis indicates complete reaction. The mixture is poured into ethyl acetate (300 ml), and washed with water (2×250 ml). The combined aqueous layers are extracted with ethyl acetate (100 ml). The combined organic layers are washed with saline, dried over magnesium sulfate and concentrated under reduced pressure to give an oil. The residue is purified by gravity filtration thru a silica gel column (2.5 cm×10 cm, 60-200μ), eluting with hexane. The appropriate fractions are pooled and concentrated to give the title compound as an oil. An analytical sample is obtained by MPLC using ethyl acetate/hexane (10/90). NMR (CDCl3, 300 MHz) 7.30, 7.16, 7.06, 6.96, 5.91, 5.16, 5.13, 4.24, 2.88 and 2.08 δ; IR (CHCl3) 2944, 1694, 1400 and 1153 cm-1 ; MS (m/e) 307, 263, 248, 172, 144 and 91, exact mass calculated for C20H21NO2 =307.1572, found 307.1565.

Workup

  1. customforming a solid
  2. temperatureThe mixture is then heated
  3. temperatureat reflux for 3.5 hr
  4. stirringthen stirred at 20°-25° overnight
  5. customthe organic layer evaporated
  6. customreaction
  7. washwashed with water (2×250 ml)
  8. extractionThe combined aqueous layers are extracted with ethyl acetate (100 ml)
  9. washThe combined organic layers are washed with saline
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customto give an oil
  13. filtrationThe residue is purified by gravity filtration
  14. washeluting with hexane
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-428d55a3bfc3402c8741e21217fb5703
Source dataset
uspto-grants-1993_01
Patent number
US05182403

Reaction notes

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