Ethyl Acetate → HCID 67823977, compound

HRID 1728363Notes

Reaction equation

HRID 1728363 reaction equation
[CH3:1][C:2]1([C:26]([O-:28])=[O:27])[CH:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([N+:14]([O-:16])=[O:15])[CH:9]=2)[C:6]([CH2:20][CH2:21][CH2:22]Br)([C:17]([O-:19])=[O:18])[CH:5]([CH3:24])[NH:4][CH:3]1[CH3:25].[ClH:29].[C:30]1([C:36]2([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]2)[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O.O>[ClH:29].[CH3:1][C:2]1([C:26]([OH:28])=[O:27])[CH:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([N+:14]([O-:16])=[O:15])[CH:9]=2)[C:6]([CH2:20][CH2:21][CH2:22][N:39]2[CH2:40][CH2:41][C:36]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[CH2:37][CH2:38]2)([C:17]([OH:19])=[O:18])[CH:5]([CH3:24])[NH:4][CH:3]1[CH3:25]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 30475044,4-Diphenylpiperidine hydrochlorideHCID 19017579HCID 19017579, compound

Product 1

HCID 67823977HCID 67823977, compoundYield 81.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 86.6 g of (-)-3-methyl-5-(3-bromopropyl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-pyridine-3,5-dicarboxylate, 50 g of 4,4-diphenylpiperidine hydrochloride and 69 g of finely powdered potassium carbonate is heated for 5 h in 300 ml of dimethyl formamide to 100° C. under a nitrogen atmosphere and with vigorous sti rring. After cooling, 500 ml of ethyl acetate and 1 l of water are added with vigorous stirring. The phases are separated; the organic phase is washed four times with water, dried over sodium sulfate and concentrated in vacuo. The residue is dissolved in 1 l of dioxane; then 15.2 ml of concentrated hydrochloric acid solution (12.5 M, d =1.19) are added, and about 200 ml of the solvent mixture are removed by distillation in vacuo. The product crystallizes spontaneously on standing at room temperature or after inoculation or trituration, and is filtered off by suction after 16 h, washed with dioxane and diisopropyl ether, and dried at 80 to 100° C. in vacuo. For further purification the crude product is dissolved in dichloromethane. After addition of 800 ml of dioxane the dichlormethane is distilled off. The product which crystallizes after inoculation on standing at room temperature for 16 h is filtered off by suction, washed with dioxane and diisopropyl ether, and dried at 100° C. in vacuo. 97 g of the title compound {m.p. 158° C. to 160° C. and [α]43622 =-39° (c=1, methanol) or [α]=-14,4 (c =1, methanol)} are obtained.

Workup

  1. temperatureAfter cooling
  2. customThe phases are separated
  3. washthe organic phase is washed four times with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue is dissolved in 1 l of dioxane
  7. additionthen 15.2 ml of concentrated hydrochloric acid solution (12.5 M, d =1.19) are added
  8. customabout 200 ml of the solvent mixture are removed by distillation in vacuo
  9. customThe product crystallizes spontaneously
  10. customon standing at room temperature
  11. filtrationafter inoculation or trituration, and is filtered off by suction after 16 h
  12. washwashed with dioxane and diisopropyl ether
  13. customdried at 80 to 100° C. in vacuo
  14. customFor further purification the crude product
  15. dissolutionis dissolved in dichloromethane
  16. additionAfter addition of 800 ml of dioxane the dichlormethane
  17. distillationis distilled off
  18. customThe product which crystallizes after inoculation
  19. filtrationis filtered off by suction
  20. washwashed with dioxane and diisopropyl ether
  21. customdried at 100° C. in vacuo

Sources & evidence

ORD record
ord-4b92d774f280414e870ce8ee9e269a35
Source dataset
uspto-grants-1994_07
Patent number
US05326772

Reaction notes

Loading…