2-Bromoanisole → HCID 18782703, compound

HRID 1420696Notes

Reaction equation

HRID 1420696 reaction equation
[CH2:1]([N:8]1[CH2:30][CH2:29][CH2:28][C:10]2([O:14][CH2:13][C:12]([Sn](CCCC)(CCCC)CCCC)=[CH:11]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[O:38][CH3:39].[Cl-].[Li+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([N:8]1[CH2:30][CH2:29][CH2:28][C:10]2([O:14][CH2:13][C:12]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=3[O:38][CH3:39])=[CH:11]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 113582-BromoanisoleHCID 433294Lithium ChlorideHCID 18782723HCID 18782723, compound

Product 1

HCID 18782703HCID 18782703, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

A mixture of 7-benzyl-3-tributylstannyl-1-oxa-7-azaspiro[4,5]dec-3-ene (Desc. 3; 1.68 g, 3.24 mmol), 2-bromoanisole (0.80 ml, 6.42 mmol), lithium chloride (0.94 g, 22 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.37 g, 0.32 mmol) in toluene (40 ml) was degassed then heated at reflux overnight (17 hours). The mixture was allowed to cool, filtered and concentrated in vacuo. The residue was dissolved in ether (100 ml) and extracted with 2M hydrochloric acid (100 ml then 25 ml). The aqueous phases were washed with more ether (100 ml), combined, basified with 4 M sodium hydroxide (70 ml) and extracted with ethyl acetate (2×50 ml). The organic phases were washed with brine (50 ml), dried (MgSO4) and concentrated. The residue was purified by flash chromatography, eluting with ethyl acetate/hexane (1:2 then 1:1), to give 7-benzyl-3-(2-methoxyphenyl)-1-oxa-7-azaspiro[4,5]dec-3-ene (0.67 g, 62%. This oil was dissolved in isopropanol and treated with excess ethereal hydrogen chloride. The mixture was concentrated in vacuo and recrystallised from isopropanol/diethyl ether to afford the title compound, m.p. 198°-201° C.; (Found: C, 69.61; H, 6.85; N, 3.62. C22H26ClNO2 0.4H2O requires C, 69.70; H, 7.13; N, 3.69%); δH (360MHz, D2O) 1.78-2.22 (4H, m), 2.98-3.26(3H, m), 3.58 (1H, m), 3.89 (3H, s, ArOCH3), 4.29 (1H, br d, NCHAHBPh), 4.43 (1H, d, J 13.1Hz, NCHAHBPh), 5.00 (2H, m, 2-CH2), 6.33 (1H, br, s, 4-H), 7.02 (1H, t, J 7.5Hz, ArH), 7.11 (1H, d, J 8.4Hz, ArH), 7.16 (1H, m, ArH), 7.39 (1H, m, ArH), 7.53 (5H, m, PhH); m/z (ES+) 336 ([M+H]+).

Workup

  1. customwas degassed
  2. temperaturethen heated
  3. temperatureat reflux overnight (17 hours)
  4. temperatureto cool
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was dissolved in ether (100 ml)
  8. extractionextracted with 2M hydrochloric acid (100 ml
  9. washThe aqueous phases were washed with more ether (100 ml)
  10. extractionextracted with ethyl acetate (2×50 ml)
  11. washThe organic phases were washed with brine (50 ml)
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated
  14. customThe residue was purified by flash chromatography
  15. washeluting with ethyl acetate/hexane (1:2

Sources & evidence

ORD record
ord-53340cde8e814da7896ee53bed002025
Source dataset
uspto-grants-2000_06
Patent number
US06071928

Reaction notes

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