Benzylamine → 11-(Phenylmethyl)-3,11-diazatricyclo[7.3.1.02,7]trideca-2,4,6-triene

HRID 272598Notes

Reaction equation

HRID 272598 reaction equation
[CH:1]12[CH2:14][CH:9]([CH:10](O)[CH:11]1O)[CH2:8][C:7]1[CH:6]=[CH:5][CH:4]=[N:3][C:2]2=1.CCOC(C)=O.[CH2:21]([NH2:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CCO.O>[CH2:21]([N:28]1[CH2:11][CH:1]2[CH2:14][CH:9]([CH2:8][C:7]3[CH:6]=[CH:5][CH:4]=[N:3][C:2]=32)[CH2:10]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Procedure

3-Aza-tricyclo[7.2.1.02,7]dodeca-2(7),3,5-triene-10,11-diol (1.16 g, 6.07 mmol) was stirred in EtOH (40 mL) and was treated with a solution of NaIO4 (1.35 g, 6.07 mmol) in H2O (20 mL). A precipitate forms and the mixture becomes a yellow slurry. After 15 min, the reaction is deemed complete (TLC EtOAc Rf 0.62), diluted with water and extracted with dichloromethane (4×50 mL). The organic layer was washed with H2O (5×50 mL) then dried through a cotton plug and concentrated to an oil. This oil was stirred in DCE (50 mL), treated with benzyl amine (650 mg, 6.07 mmol) then sodium triacetoxyborohydride NaBH(OAc)3 (4.12 g, 19.4 mmol). The mixture was stirred 7 h, then was quenched by addition to saturated sodium carbonate (Na2CO3) solution and EtOAc (˜75 mL each). After stirring 20 min., the layers were separated and the aqueous layer was extracted with EtOAc (2×50 mL). The organic layer was washed with H2O (50 mL) and saturated aqueous NaCl solution (50 mL) then dried over Na2SO4. Filtration and concentration affords an oil, 1.2 g which was purified by chromatography on silica gel eluting with 50% EtOAc/hexanes to provide pure product as an oil, 802 mg (50%). (TLC EtOAc Rf 0.68); 1H NMR (400 MHz, CDCl3) δ 8.30 (dd, J=4.7, 0.6 Hz, 1H), 7.40 (d, J=7.7 Hz, 1H), 7.13–7.07 (m, 4H), 6.85 (m, 2H), 3.35 (AB q, ΔAB=27.2, J=13.8 Hz, 2H), 3.08 (s, 1H), 3.02 (dd, J=17.3, 7.0 Hz, 1H), 2.92 (d, J=10.6 Hz, 1H), 2.81 (d, J=10.6 Hz, 1H), 2.74 (d, J=17.3 Hz, 1H) 3.34 (br d, J=10.6 Hz, 2H), 2.17 (br s, 1H), 1.90 (d, J=3.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 160.8, 145.6, 139.2, 134.7, 134.2, 128.1, 128.0, 126.6, 121.0, 62.3, 60.8, 58.9, 38.4, 34.2, 29.8, 28.4; APCl MS m/z 265.1 (M)+.

Workup

  1. extractionextracted with dichloromethane (4×50 mL)
  2. washThe organic layer was washed with H2O (5×50 mL)
  3. customthen dried through a cotton plug
  4. concentrationconcentrated to an oil
  5. stirringThe mixture was stirred 7 h
  6. customwas quenched by addition to saturated sodium carbonate (Na2CO3) solution and EtOAc (˜75 mL each)
  7. stirringAfter stirring 20 min.
  8. customthe layers were separated
  9. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
  10. washThe organic layer was washed with H2O (50 mL) and saturated aqueous NaCl solution (50 mL)
  11. dry with materialthen dried over Na2SO4
  12. filtrationFiltration and concentration
  13. customaffords an oil, 1.2 g which
  14. customwas purified by chromatography on silica gel eluting with 50% EtOAc/hexanes
  15. customto provide pure product as an oil, 802 mg (50%)

Sources & evidence

ORD record
ord-9d31ea8e44f948268631d8207e889500
Source dataset
uspto-grants-2008_11
Patent number
US07456177B2

Reaction notes

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