2-Chloro-N,N-dimethylethylamine → HCID 14773544, compound

HRID 1165130Notes

Reaction equation

HRID 1165130 reaction equation
[CH3:1][O:2][N:3]1[CH:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:8][C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]=2[NH:5][C:4]1=[O:20].O1CCCC1.C([Li])CCC.[CH3:31][N:32]([CH3:36])[CH2:33][CH2:34]Cl>O>[CH3:31][N:32]([CH2:33][CH2:34][N:5]1[C:6]2[CH:19]=[CH:18][CH:17]=[CH:16][C:7]=2[CH2:8][CH:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:3]([O:2][CH3:1])[C:4]1=[O:20])[CH3:36]

Participants

6

Reactant 4

HCID 79012-Chloro-N,N-dimethylethylamine2×HCID 8028TetrahydrofuranHCID 14773543HCID 14773543, compoundHCID 178418339Butyllithium

Product 1

HCID 14773544HCID 14773544, compoundYield 162%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred, chilled (-78° C.) solution of (±) -3-methoxy-4-phenyl-1,3,4,5-tetrahydro-2H-1,3-benzodiazepine-2-one (5.0 g, 0.019 mol) of Example 1c and tetrahydrofuran (200 ml) was added n-butyllithium (9.1 ml of a 2.5 M solution in hexanes, 0.023 mol) (nitrogen atmosphere). The solution was stirred and cooled for 50 minutes, then 2-dimethylaminoethylchloride (10.22 .g, 0.095 mol) was added and the solution was allowed to warm to room temperature. The mixture was stirred and heated to 45° C. for 48 hours, with additional 2-dimethylaminoethylchloride added as follows: 16.5 hours, 14.0 g, 0.13 mol; 24 hours, 14.0 g, 0.13 mol. The mixture was then heated to reflux for 2 hours, allowed to cool, and water (400 ml) was added to quench the reaction. The tetrahydrofuran was removed in vacuo and the resulting oily aqueous phase was extracted twice with 250 ml portions of dichloromethane. The combined organic phase was washed twice with water (300 ml portions), once with saturated sodium chloride (200 ml), and was dried (Na2SO4), filtered, and concentrated to give a solid (10.45 g). The solid was purified by preparative HPLC (Waters Associates Prep LC/System 500, silica gel sample loaded in dichloromethane, eluted with 3:1 ethyl acetate:methanol). The appropriate fractions were combined, evaporated, dissolved in dichloromethane, filtered to remove all insoluble material, and concentrated to yield 1.70 g of a solid (26%). The products of several similar reactions were combined and repurified by preparative HPLC, as above, to yield 2.95 g of a solid, which was recrystallized from dichloromethane/ether to afford 2.39 g (26%) of (±) -1-[2-(N,N-dimethylamino)ethyl]-3-methoxy-4-phenyl-1,3,4,5-tetrahydro-2H-1,3-benzodiazepine-2-one,m.p.127°-128° C.

Workup

  1. temperaturecooled for 50 minutes
  2. stirringThe mixture was stirred
  3. additionadded
  4. custom16.5 hours, 14.0 g, 0.13 mol
  5. custom24 hours, 14.0 g, 0.13 mol
  6. temperatureThe mixture was then heated
  7. temperatureto reflux for 2 hours
  8. temperatureto cool
  9. customto quench
  10. customthe reaction
  11. customThe tetrahydrofuran was removed in vacuo
  12. extractionthe resulting oily aqueous phase was extracted twice with 250 ml portions of dichloromethane
  13. washThe combined organic phase was washed twice with water (300 ml portions), once with saturated sodium chloride (200 ml)
  14. dry with materialwas dried (Na2SO4)
  15. filtrationfiltered
  16. concentrationconcentrated

Sources & evidence

ORD record
ord-34a9184699ce405bbedc1a78047eaa91
Source dataset
uspto-grants-1990_03
Patent number
US04908360

Reaction notes

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