Chlorobenzene → HCID 11818272, compound

HRID 854065Notes

Reaction equation

HRID 854065 reaction equation
Cl[CH2:2][CH2:3][NH:4][CH2:5][CH2:6]Cl.[O:8]1[C:13]2[CH:14]=[CH:15][CH:16]=[C:17]([NH2:18])[C:12]=2[O:11][CH2:10][CH2:9]1.[C:19](=[O:22])(O)[O-].[Na+].[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl[C:31]1C=CC=C[CH:32]=1>O1CCCC1.C(OCC)(=O)C>[O:8]1[C:13]2[CH:14]=[CH:15][CH:16]=[C:17]([N:18]3[CH2:6][CH2:5][N:4]([C@H:31]([CH3:32])[CH2:19][OH:22])[CH2:3][CH2:2]3)[C:12]=2[O:11][CH2:10][CH2:9]1

Participants

8

Reactant 5

HCID 7964ChlorobenzeneHCID 9533Bis(2-chloroethyl)amineHCID 516892Sodium BicarbonateHCID 117883872,3-Dihydro-1,4-benzodioxin-5-amineHCID 21226445Aluminium lithium hydride

Product 1

HCID 11818272HCID 11818272, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A free base of bis(2-chloroethyl)amine (28.4 g; 0.2 mol) is liberated from its hydrochloride salt as described in Example IV and mixed with a solution of (S)-2-[(trifluoromethylsulfonyl)oxy] propionate (20 g; 0.08 mol) in chlorobenzene (150 mL). The mixture is stirred for 3 hours at room temperature, and the resulting thick slurry is washed with water (100 mL) and 10% sodium bicarbonate (100 mL). The organic phase is transferred to a flask containing 2,3-dihydro-1,4-benzodioxin-5-amine (9.6 g; 0.064 mol) and the reaction mixture is allowed to reflux upon stirring for 18 hours. A small amount of yellow precipitate appears. The mixture is cooled to room temperature and agitated with 10% aqueous sodium bicarbonate (55 mL) for 1 hour. The organic layer is separated, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue is dissolved in tetrahydrofuran (50 mL) and added dropwise to a stirred suspension of lithium aluminum hydride (9.1 g; 0.24 mol) in tetrahydrofuran (50 mL). The mixture is heated to 40° C. for 90 minutes, cooled, and decomposed by dropwise addition of ethyl acetate (200 mL). The product is then extracted with 2N hydrochloric acid (500 mL), the aqueous portion is washed three times with ethyl acetate (150 mL) and rendered basic with 10N sodium hydroxide to re-extract the product with ethyl acetate (2×200 mL). The combined extracts are washed with brine, dried over sodium sulfate, filtered and evaporated in vacuo. The residual oil crystallizes upon standing, and in TLC analysis (ethyl acetate-hexane 3:2) co-spots with the alcohol of Example III. Spectroscopic data and enantiomeric purity are identical to those presented in Example Ill. Overall yield 9.1 g (51%) based on 2,3-dihydro-1,4-benzodioxin-5-amine.

Workup

  1. washthe resulting thick slurry is washed with water (100 mL) and 10% sodium bicarbonate (100 mL)
  2. customThe organic phase is transferred to a flask
  3. temperatureto reflux
  4. stirringupon stirring for 18 hours
  5. temperatureThe mixture is cooled to room temperature
  6. customThe organic layer is separated
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue is dissolved in tetrahydrofuran (50 mL)
  11. temperatureThe mixture is heated to 40° C. for 90 minutes
  12. temperaturecooled
  13. extractionThe product is then extracted with 2N hydrochloric acid (500 mL)
  14. washthe aqueous portion is washed three times with ethyl acetate (150 mL)
  15. extractionto re-extract the product with ethyl acetate (2×200 mL)
  16. washThe combined extracts are washed with brine
  17. dry with materialdried over sodium sulfate
  18. filtrationfiltered
  19. customevaporated in vacuo
  20. customThe residual oil crystallizes

Sources & evidence

ORD record
ord-9323990d9aee415cae730c68f6760847
Source dataset
uspto-grants-2007_08
Patent number
US07256289B2

Reaction notes

Loading…