Chloroacetonitrile → HCID 14349026, compound

HRID 414813Notes

Reaction equation

HRID 414813 reaction equation
[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].ClC1C=C(C=CC=1)OC1C2C=CC=CC=2CCNC1.ClCC#N.C(=O)(O)[O-].[Na+].[Cl:35][C:36]1[CH:37]=[C:38]([CH:54]=[CH:55][CH:56]=1)[O:39][CH:40]1[C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=2[CH2:44][CH2:43][N:42]([CH2:51][C:52]#[N:53])[CH2:41]1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>CN(C=O)C.C1COCC1.CCOCC>[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[NH2:53][CH2:52][CH2:51][N:42]1[CH2:41][CH:40]([O:39][C:38]2[CH:54]=[CH:55][CH:56]=[C:36]([Cl:35])[CH:37]=2)[C:46]2[CH:47]=[CH:48][CH:49]=[CH:50][C:45]=2[CH2:44][CH2:43]1

Participants

9

Reactant 5

HCID 7856ChloroacetonitrileHCID 516892Sodium BicarbonateHCID 14348993HCID 14348993, compoundHCID 15137765HCID 15137765, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 14349026HCID 14349026, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

A mixture of 1-(m-chlorophenoxy)-2,3,4,5-tetrahydro-3-benzazepine of Example 4 (8.0 g, 0.029 mole), chloroacetonitrile (4.4 g, 0.058 mole) and sodium bicarbonate (10 g, 0.12 mole in DMF (100 ml) was stirred at 65° C. for 2.5 hours. The mixture was concentrated to an oil which was stirred with water and extracted with ether. The organic extracts were washed twice with water and dried (saturated NaCl, anhydrous MgSO4). The solution was filtered and concentrated to an oil (8 g) which was extracted with boiling hexanes and concentrated to a light solid (5.4 g, 62%, m.p. 89°-95° C.). A solution of 1-(m-chlorophenoxy)-3-cyanomethyl-2,3,4,5-tetrahydro-3-benzazepine (5.1 g, 0.017 mole) in THF (50 ml) was dropped into a stirred suspension of LiAlH4 (2.6 g, 0.068 mole) in THF (100 ml). After stirring three hours at ambient temperature, the reaction mixture was cooled, diluted with ether, then quenched by dropwise addition of saturated NH4Cl. The mixture was filtered, and the organic filtrate was washed twice with water and dried (saturated NaCl, anhydrous MgSO4). The solution was filtered and concentrated to an oil (3.7 g,) which was converted using the procedure of Example 1 to the dioxalate salt (5.5 g, 65%, d 150°-155° C.). This material was twice recrystallized from a 20:1 solution of ethyl acetate/methanol to yield 3-(2-aminoethyl)-1-(m-chlorophenoxy)-2,3,4,5-tetrahydro-3-benzazepine dioxalate, d 172°-173° C.

Workup

  1. concentrationThe mixture was concentrated to an oil which
  2. stirringwas stirred with water
  3. extractionextracted with ether
  4. washThe organic extracts were washed twice with water
  5. dry with materialdried (saturated NaCl, anhydrous MgSO4)
  6. filtrationThe solution was filtered
  7. concentrationconcentrated to an oil (8 g) which
  8. extractionwas extracted with boiling hexanes
  9. concentrationconcentrated to a light solid (5.4 g, 62%, m.p. 89°-95° C.)
  10. stirringAfter stirring three hours at ambient temperature
  11. temperaturethe reaction mixture was cooled
  12. customquenched by dropwise addition of saturated NH4Cl
  13. filtrationThe mixture was filtered
  14. washthe organic filtrate was washed twice with water
  15. dry with materialdried (saturated NaCl, anhydrous MgSO4)
  16. filtrationThe solution was filtered
  17. concentrationconcentrated to an oil (3.7 g,) which
  18. customto the dioxalate salt (5.5 g, 65%, d 150°-155° C.)
  19. customThis material was twice recrystallized from a 20:1 solution of ethyl acetate/methanol

Sources & evidence

ORD record
ord-631261f5363d4c24b47f10215e5e7b54
Source dataset
uspto-grants-1988_12
Patent number
US04794181

Reaction notes

Loading…