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

HRID 1109149Notes

Reaction equation

HRID 1109149 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][N:19]3[C:24](=[O:25])[CH2:23][C:22]([CH3:27])([CH3:26])[CH2:21][C:20]3=[O:28])[C:6]=2[CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:36][N:37]([CH3:41])[C:38]([Cl:40])=[O:39].Cl>C1(C)C=CC=CC=1.CN(C)C1C=CN=CC=1.C(Cl)Cl.C(OCC)(=O)C>[ClH:40].[CH3:36][N:37]([CH3:41])[C:38](=[O:39])[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][N:19]3[C:20](=[O:28])[CH2:21][C:22]([CH3:26])([CH3:27])[CH2:23][C:24]3=[O:25])[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 131718491rac-cis-1-[4-(6-hydroxy-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indol-3-yl)-butyl]-4,4-dimethyl-piperidine-2,6-dione

Product 1

HCID 131718489rac-cis-3-[4-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)-butyl]-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indol-6-yl dimethylcarbamate hydrochlorideYield 62.5%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolventHCID 21226138Dichloromethane ethylacetateSolvent

Procedure

5.0 g (13.0 mmol) of rac-cis-1-[4-(6-hydroxy-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indol-3-yl)-butyl]-4,4-dimethyl-piperidine-2,6-dione were dissolved in 250 ml of toluene. The solution was treated with 2.76 g (3.8 ml, 27 mmol) of triethyl-amine and 1.68 g (1.43 ml, 16 mmol) of dimethylcarbamoyl chloride and 250 mg of 4-dimethylaminopyridine and stirred under an argon atmosphere overnight in an oil bath 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 resulting brown oil (6.5 g) was chromatographed over a 30-fold amount of silica gel. The uniform eluates obtained in a thin-layer chromatogram using methylene chloride/ethyl acetate 1:1 were pooled and evaporated. The yellow oily base obtained (4.0 g) was converted into the hydrochloride in the usual manner, whereby there were obtained 4.0 g (62%) of rac-cis-3 -[4-(4,4-dimethyl-2,6-dioxo-piperidin-1-yl)-butyl]-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indol-6-yl dimethylcarbamate hydrochloride as yellowish crystals of m.p. 190°-192° (dec.).

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 resulting brown oil (6.5 g) was chromatographed over a 30-fold amount of silica gel
  6. customThe uniform eluates obtained in a thin-layer chromatogram
  7. customevaporated
  8. customThe yellow oily base obtained (4.0 g)

Sources & evidence

ORD record
ord-2eb2f75d557047699b16a59aa336a495
Source dataset
uspto-grants-1994_06
Patent number
US05318966

Reaction notes

Loading…