Dimethylcarbamoyl Chloride → rac-cis-3-[6-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)hexyl]-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indol-6-yl dimethylcarbamate

HRID 1109154Notes

Reaction equation

HRID 1109154 reaction equation
[OH:1][C:2]1[C:14]2[CH2:13][CH2:12][C@H:11]3[C@H:7]([CH2:8][CH2:9][N:10]3[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]3[C:26](=[O:27])[CH2:25][C:24]([CH3:29])([CH3:28])[CH2:23][C:22]3=[O:30])[C:6]=2[CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:38][N:39]([CH3:43])[C:40](Cl)=[O:41].C(Cl)Cl.C(OCC)(=O)C>C1(C)C=CC=CC=1.CN(C)C1C=CN=CC=1>[CH3:38][N:39]([CH3:43])[C:40](=[O:41])[O:1][C:2]1[C:14]2[CH2:13][CH2:12][C@H:11]3[C@H:7]([CH2:8][CH2:9][N:10]3[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]3[C:22](=[O:30])[CH2:23][C:24]([CH3:28])([CH3:29])[CH2:25][C:26]3=[O:27])[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 21226138Dichloromethane ethylacetateHCID 131718497rac-cis-1-[6-(6-hydroxy-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indol-3-yl)hexyl]-4,4-dimethylpiperidine-2,6-dione

Product 1

HCID 131718498rac-cis-3-[6-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)hexyl]-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indol-6-yl dimethylcarbamateYield 51.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolvent

Procedure

5.0 g (12.12 mmol) of rac-cis-1-[6-(6-hydroxy-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indol-3-yl)hexyl]-4,4-dimethyl-piperidine-2,6-dione were dissolved in 200 ml of toluene, whereupon the solution was treated with 2.57 g (3.55 ml, 25.45 mmol) of triethylamine, 1.56 g (1.33 ml, 14.53 mmol) of dimethylcarbamoyl chloride and 250 mg of 4-dimethylamino-pyridine and stirred in an oil bath under an argon atmosphere overnight at an oil bath temperature of 110°. After cooling the organic phase was washed in succession with water, sodium bicarbonate solution and water, dried over magnesium sulphate and evaporated. The brown oil obtained (6.0 g) was chromatographed on a 30-fold amount of silica gel. After concentration of the eluates obtained using methylene chloride/ethyl acetate 1:1 there were obtained 3.0 g of yellowish rac-cis-3-[6-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)hexyl]-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indol-6-yl dimethylcarbamate, which was converted into the hydrochloride in the usual manner. There were obtained 3.0 g (48%) of hydrochloride in the form of yellowish crystals of m.p. 144.5°-146°.

Workup

  1. temperatureAfter cooling the organic phase
  2. washwas washed in succession with water, sodium bicarbonate solution and water
  3. dry with materialdried over magnesium sulphate
  4. customevaporated
  5. customThe brown oil obtained (6.0 g)
  6. customwas chromatographed on a 30-fold amount of silica gel
  7. customAfter concentration of the eluates obtained

Sources & evidence

ORD record
ord-e473c1a412d94dfb9101f6118ee1af76
Source dataset
uspto-grants-1994_06
Patent number
US05318966

Reaction notes

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