(Chloromethyl)cyclopropane → HCID 14349008, compound

HRID 704668Notes

Reaction equation

HRID 704668 reaction equation
[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[Cl:7][C:8]1[CH:9]=[C:10]([CH:23]=[CH:24][CH:25]=1)[O:11][CH:12]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[CH2:16][CH2:15][NH:14][CH2:13]1.Cl[CH2:27][CH:28]1[CH2:30][CH2:29]1.C(=O)(O)[O-].[Na+]>CN(C=O)C>[C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[Cl:7][C:8]1[CH:9]=[C:10]([CH:23]=[CH:24][CH:25]=1)[O:11][CH:12]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[CH2:16][CH2:15][N:14]([CH2:27][CH:28]2[CH2:30][CH2:29]2)[CH2:13]1

Participants

5

Reactant 3

HCID 80013(Chloromethyl)cyclopropaneHCID 516892Sodium BicarbonateHCID 14348993HCID 14348993, compound

Product 1

HCID 14349008HCID 14349008, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-(m-chlorophenoxy)-2,3,4,5-tetrahydro-3-benzazepine of Example 4, (7.0 g. 0.026 mole), chloromethylcyclopropane (4.6 g, 0.051 mole) and sodium bicarbonate (8.4 g, 0.10 mole) in DMF (85 ml) was warmed at 80°-90° C. for four hours. The reaction mixture was cooled, then concentrated under high vacuum to an oil which was stirred with water and extracted with ether. The ether extracts were twice washed with water and dried (saturated NaCl, anhydrous MgSO4). The solution was filtered, then concentrated to an oil which was dissolved in ether and then converted to the oxalate salt (7 g, mp 80°-95° C.) using the procedure of Example 1. This material was rebasified, then passed through a silica gel dry column with ethyl acetate as eluent. The desired product was extracted with ethyl acetate then concentrated to an oil (3.3 g). This oil was converted to the oxalate salt using the procedure of Example 1 and then immediately recrystallized from a 20:1 solution of ethyl acetate/methanol to yield 1-(m-chlorophenoxy)-3-cyclopropylmethyl-2,3,4,5-tetrahydro-3-benzazepine oxalate, (3.1 g, d 100°-101° C.)

Workup

  1. temperaturewas warmed at 80°-90° C. for four hours
  2. temperatureThe reaction mixture was cooled
  3. concentrationconcentrated under high vacuum to an oil which
  4. extractionextracted with ether
  5. washThe ether extracts were twice washed with water
  6. dry with materialdried (saturated NaCl, anhydrous MgSO4)
  7. filtrationThe solution was filtered
  8. concentrationconcentrated to an oil which
  9. dissolutionwas dissolved in ether
  10. dry with materialdry column with ethyl acetate as eluent
  11. extractionThe desired product was extracted with ethyl acetate
  12. concentrationthen concentrated to an oil (3.3 g)
  13. customimmediately recrystallized from a 20:1 solution of ethyl acetate/methanol

Sources & evidence

ORD record
ord-d1a6110e56e740fd8109cef2a05ec8b9
Source dataset
uspto-grants-1991_01
Patent number
US04988690

Reaction notes

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