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 893729Notes

Reaction equation

HRID 893729 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=O.[NH2:7][CH2:8][CH2:9][NH:10][CH2:11][CH:12]1[O:17][C:16]2[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=2[O:14][CH2:13]1.C(N([CH:28]([CH3:30])[CH3:29])CC)(C)C>ClCCl.CN(C=O)C>[O:17]1[C:16]2[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=2[O:14][CH2:13][CH:12]1[CH2:11][NH:10][CH2:9][CH2:8][NH:7][C:15]([C:16]12[C:28]([CH3:29])([CH3:30])[CH:20]([CH2:19][CH2:18]1)[CH2:2][C:1]2=[O:5])=[O:14]

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 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-carboxamideYield 67.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To 2.0 g (10 mmole) (-)-ketopinic acid in 100 ml of dichloromethane was added 2.0 ml (23 mmole) oxalyl choride and 2 drops of DMF. The mixture was stirred for two hours at room temperature and then concentrated to dryness in vacuum. It was redissolved in 50 ml of methylenechloride and added to a cold solution of 2.1 g (10 mmole) 2-[N-(2-aminoethyl)]aminomethyl-2,3-dihydrobenzodioxin and 1.3 g (10 mmole) diisopropylethylamine in 100 ml of dichloromethane. The mixture was stirred at room temperature overnight. It was then washed with saturated aqueous sodium bicarbonate, with saturated sodium chloride, dried over sodium sulfate, filtered and evaporated in vacuum. The residue was column chromatographed on 100 g of silica gel with chloroform as eluant, and the product crystallized from 75 ml of isopropanol with the addition of 4 ml 4 N HCl/isopropyl alcohol and 225 ml of diethyl ether to produce 1.25 g of the title compound as the hydrochloride, quarter hydrate, m.p. 164°-166° C., [α]D25 =-31.3 (MeOH).

Workup

  1. concentrationconcentrated to dryness in vacuum
  2. dissolutionIt was redissolved in 50 ml of methylenechloride
  3. stirringThe mixture was stirred at room temperature overnight
  4. washIt was then washed with saturated aqueous sodium bicarbonate, with saturated sodium chloride
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuum
  8. customchromatographed on 100 g of silica gel with chloroform as eluant
  9. customthe product crystallized from 75 ml of isopropanol with the addition of 4 ml 4 N HCl/isopropyl alcohol and 225 ml of diethyl ether

Sources & evidence

ORD record
ord-9dd75add16f2455fb553cc42765150e8
Source dataset
uspto-grants-1992_06
Patent number
US05126367

Reaction notes

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