Ammonium Chloride → HCID 54493135, compound

HRID 1651623Notes

Reaction equation

HRID 1651623 reaction equation
[Cl:1][C:2]1[CH2:3][N:4]=[CH:5][C:6]2([CH3:19])[CH:17]([CH3:18])[CH:15]3[CH2:16][C:10]4=[C:11]([NH:14]3)[CH2:12][CH2:13][C:7]2=[C:8]4[CH:9]=1.C(N(C(C)C)CC)(C)C.[CH:29]1([CH2:32]Br)[CH2:31][CH2:30]1.[Cl-].[NH4+]>C(OCC)(=O)C.CN(C)C=O>[Cl:1][C:2]1[CH2:3][N:4]=[CH:5][C:6]2([CH3:19])[CH:17]([CH3:18])[CH:15]3[CH2:16][C:10]4=[C:11]([N:14]3[CH2:32][CH:29]3[CH2:31][CH2:30]3)[CH2:12][CH2:13][C:7]2=[C:8]4[CH:9]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81503Bromomethylcyclopropane2×HCID 81531DiisopropylethylamineHCID 73656239HCID 73656239, compound

Product 1

HCID 54493135HCID 54493135, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 2.2 g of 10-chloro-6,12-dimethyl-1,2,3,4,5,6-hexahydro-2,6-methano-9H-pyrrolo[3,2-h][3]benzazocine and 40 ml of dimethylformamide was added 3.2 ml of diisopropylethyl amine and 1.07 ml of cyclopropylmethyl bromide, under nitrogen. The reaction mixture was warmed in an oil bath maintained at 70°-77° C. Additional cyclopropylmethyl bromide (0.16 ml) was added, warming continued for a total of 3 hr, and the solution was poured into dilute aqueous ammonium chloride solution and ethyl acetate. The layers were separated and the aqueous layer extracted with ethyl acetate and ether. The combined organic layers were washed with brine, dried over anhydrous potassium carbonate and filtered. The filtrate was concentrated. The residue was purified by flash column chromatography (silica gel, 2% triethylamine/0-5% methanol/ethyl acetate) followed by recrystallization from ether/dichloromethane/pentane to afford 0.97 g (32%) of product. The product was combined with products from two other reactions. The combined material was recrystallized from dichloromethane and the sublimed (175°-180° C., about 0.2 mm) to give the analytical sample, mp 187°-190° C.

Workup

  1. temperatureThe reaction mixture was warmed in an oil bath
  2. temperaturemaintained at 70°-77° C
  3. temperaturewarming
  4. customcontinued for a total of 3 hr
  5. customThe layers were separated
  6. extractionthe aqueous layer extracted with ethyl acetate and ether
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over anhydrous potassium carbonate
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated
  11. customThe residue was purified by flash column chromatography (silica gel, 2% triethylamine/0-5% methanol/ethyl acetate)
  12. customfollowed by recrystallization from ether/dichloromethane/pentane

Sources & evidence

ORD record
ord-3826426ffccd45f8ae65d69f6cd3ddaf
Source dataset
uspto-grants-1990_05
Patent number
US04929622

Reaction notes

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