Oxalyl chloride → (+)-N-[2-[[(2,3-Dihydro-1,4-benzodioxin-2-yl)methyl]amino]ethyl]-7,7-dimethyl-2-oxobicyclo[2,2,1]heptane-1-carboxamide

HRID 893728Notes

Reaction equation

HRID 893728 reaction equation
[CH3:1][C:2]1([CH3:15])[C:6]2([CH2:10]S(Cl)(=O)=O)[C:7]([CH2:9][CH:3]1[CH2:4][CH2:5]2)=[O:8].C(Cl)(=O)C(Cl)=[O:18].[NH2:22][CH2:23][CH2:24][NH:25][CH2:26][CH:27]1[O:32][C:31]2[CH:33]=[CH:34][CH:35]=[CH:36][C:30]=2[O:29][CH2:28]1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[O:32]1[C:31]2[CH:33]=[CH:34][CH:35]=[CH:36][C:30]=2[O:29][CH2:28][CH:27]1[CH2:26][NH:25][CH2:24][CH2:23][NH:22][C:10]([C:6]12[C:2]([CH3:15])([CH3:1])[CH:3]([CH2:4][CH2:5]1)[CH2:9][C:7]2=[O:8])=[O:18]

Participants

6

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 26579910-Camphorsulfonyl chlorideHCID 146529492-[N-(2-aminoethyl)]aminomethyl-2,3-dihydrobenzodioxin

Product 1

HCID 19891064(+)-N-[2-[[(2,3-Dihydro-1,4-benzodioxin-2-yl)methyl]amino]ethyl]-7,7-dimethyl-2-oxobicyclo[2,2,1]heptane-1-carboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(+)-Ketopinic acid (900 mg, 5.0 mmole), prepared from (+)-10-camphorsulfonyl chloride by the procedure of Bartlett and Knox, Org. Syn., 45, p. 55, was converted to the acid chloride by treatment of a solution of the compound in 50 ml of methylene chloride with 1.0 ml (11.5 mmole) of oxalyl chloride. After stirring for 2 hours at room temperature, the mixture was concentrated in vacuum. It was then redissolved in 50 ml of methylenechloride and added at 0° C. to a solution of 1.04 g (10 mmole) of 2-[N-(2-aminoethyl)]aminomethyl-2,3-dihydrobenzodioxin and 1.3 g (10 mmole) of diisopropylethylamine in 50 ml of dichloromethane. After stirring overnight at room temperature, the mixture was washed with saturated sodium bicarbonate solution, with saturated sodium chloride, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was column chromatographed on 75 g of silica gel with chloroform as eluant and the title compound crystallized from isopropanol with the addition of 4 N HCl/isopropyl alcohol and 3 volumes of diethyl ether. This procedure gave 835 mg of title compound as the monohydrochloride, m.p. 172°-173° C., with an [α]D25 =+32.7 (MeOH).

Workup

  1. concentrationthe mixture was concentrated in vacuum
  2. dissolutionIt was then redissolved in 50 ml of methylenechloride
  3. stirringAfter stirring overnight at room temperature
  4. washthe mixture was washed with saturated sodium bicarbonate solution, with saturated sodium chloride
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuum
  8. customchromatographed on 75 g of silica gel with chloroform as eluant
  9. customthe title compound crystallized from isopropanol with the addition of 4 N HCl/isopropyl alcohol and 3 volumes of diethyl ether

Sources & evidence

ORD record
ord-4af8689d729349fe90129fcd35a816be
Source dataset
uspto-grants-1992_06
Patent number
US05126367

Reaction notes

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