Triethylamine → trans-N-Methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-4,5-dichloro-2-thienylacetic acid amide hydrochloride

HRID 615447Notes

Reaction equation

HRID 615447 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9](Cl)=[O:10])[S:5][C:6]=1[Cl:7].[CH3:12][NH:13][C@@H:14]1[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]1[N:20]1[CH2:24][CH2:23][CH2:22][CH2:21]1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl>[ClH:1].[CH3:12][N:13]([C@@H:14]1[CH2:19][CH2:18][CH2:17][CH2:16][C@H:15]1[N:20]1[CH2:24][CH2:23][CH2:22][CH2:21]1)[C:9](=[O:10])[CH2:8][C:4]1[S:5][C:6]([Cl:7])=[C:2]([Cl:1])[CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 133774614,5-Dichloro-2-thienylacetic acid chlorideHCID 13377463Cyclohexanamine, N-methyl-2-(1-pyrrolidinyl)-, trans-

Product 1

HCID 70489484trans-N-Methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-4,5-dichloro-2-thienylacetic acid amide hydrochlorideYield 57%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A solution of 1,61 g (7,01 mmoles) of 4,5-dichloro-2-thienylacetic acid chloride (formula (II); X=4-Cl, Y=5-Cl, Z=Cl) in 15 ml of absolute chloroform is dropped to a solution of 1,24 g (6,80 mmoles) of trans-N-methyl-2-(1-pyrrolidinyl)cyclohexylamine (formula III; R=methyl, ##STR7## and 0,69 g (6,80 mmoles) of triethylamine in 60 ml of absolute chloroform for 15 minutes at room temperature and then stirred 18 hours at room temperature. Thereafter the reaction solution is shaken out with saturated solution of sodium hydrogen carbonate, the organic phase is washed with water, dried over sodium sulfate and evaporated. The oily residue consisting of the crude base of formula (I) and some ether-insoluble by-product is taken up with 30 ml of ether, filtered over activated charcoal and HCl-gas is introduced into the solution. The precipitated crystalline hydrochloride is sucked off, dissolved in 4 ml of methanol, precipitated with 50 ml of wet ether, sucked off and the operation is repeated once. The colorless crystals are dried at 13,3 Pa and room temperature for 5 hours. Thus the non-hygroscopic hemihydrate of the hydrochloride is obtained. Yield 57%. M.p. 216°-218° C. The compound free of crystal water obtained by drying in vacuo at 13,3 Pa and 140° C. is hygroscopic.

Workup

  1. washthe organic phase is washed with water
  2. dry with materialdried over sodium sulfate
  3. customevaporated
  4. filtrationfiltered over activated charcoal and HCl-gas
  5. additionis introduced into the solution
  6. dissolutiondissolved in 4 ml of methanol
  7. customprecipitated with 50 ml of wet ether
  8. customThe colorless crystals are dried at 13,3 Pa and room temperature for 5 hours

Sources & evidence

ORD record
ord-f994442b0075473bb0f64f7909593295
Source dataset
uspto-grants-1985_02
Patent number
US04499286

Reaction notes

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