Water → 3-Benzyl-8,8-dimethoxy-3-aza-bicyclo[3.2.1]oct-6-ene

HRID 1295492Notes

Reaction equation

HRID 1295492 reaction equation
O.[Na].[CH2:3]([N:10]1[CH2:16][C:15]2(Cl)[C:17]([O:20][CH3:21])([O:18][CH3:19])[C:12](Cl)([C:13](Cl)=[C:14]2Cl)[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(O)(C)(C)C>O1CCOCC1>[CH2:3]([N:10]1[CH2:16][CH:15]2[C:17]([O:20][CH3:21])([O:18][CH3:19])[CH:12]([CH:13]=[CH:14]2)[CH2:11]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6386tert-ButanolHCID 5360545Sodium2×HCID 589077513-Benzyl-1,5,6,7-tetrachloro-8,8-dimethoxy-3-aza-bicyclo[3.2.1]oct-6-ene

Product 1

HCID 589077523-Benzyl-8,8-dimethoxy-3-aza-bicyclo[3.2.1]oct-6-eneYield 85.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a 3 L 3NRB equipped with a thermometer, addition funnel and water condenser was added dioxane (1000 mL) then sodium (44.7 g, 1.94 mol). Upon heating under reflux (T ˜100° C.), the sodium became a dispersed immiscible liquid. While maintaining this gentle reflux, a solution of 3-benzyl-1,5,6,7-tetrachloro-8,8-dimethoxy-3-aza-bicyclo[3.2.1]oct-6-ene (52.5 g, 0.132 mol), t-butanol (160 mL, 1.67 mol) and dioxane (150 mL) was added dropwise via the addition funnel over 30 min and heat continued overnight. Upon cooling to 70° C., the residual unreacted sodium was quenched with MeOH (150 mL) then water (1 L). The dioxane and MeOH were then removed in vacuo. The product was extracted from the aqueous layer with EtOAc (3×300 mL), washed with saturated aqueous NaCl solution (1×300 mL), dried over Na2SO4, filtered and concentrated to yield a dark brown oil (29.2 g, 85%). (TLC 40% EtOAc/hexanes Rf 0.35); 1H NMR (400 MHz, CDCl3) δ 7.28–7.20 (5H), 6.01 (t, J=1.6 Hz, 2H), 3.65 (s, 2H), 3.23 (s, 3H), 3.17 (s, 3H), 2.63 (s, 2H), 2.57 (AB d, J=10.1 Hz, 2H), 2.44 (AB d, J=10.1 Hz, 2H); GCMS m/z 259 (M)+; APCI MS m/z 260.2 (M+1)+.

Workup

  1. temperatureUpon heating
  2. temperatureWhile maintaining this gentle reflux
  3. temperatureheat
  4. temperatureUpon cooling to 70° C.
  5. customthe residual unreacted sodium was quenched with MeOH (150 mL)
  6. customThe dioxane and MeOH were then removed in vacuo
  7. extractionThe product was extracted from the aqueous layer with EtOAc (3×300 mL)
  8. washwashed with saturated aqueous NaCl solution (1×300 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-dc8b1b6cf5e344bdb1e9cee88bc9912c
Source dataset
uspto-grants-2007_07
Patent number
US07241887B2

Reaction notes

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