Triethylamine → N-(1-norbornyl-2-pyrrolidylmethyl)-2-methoxy-5-methylsulphonyl benzamide

HRID 652760Notes

Reaction equation

HRID 652760 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([S:12]([CH3:15])(=[O:14])=[O:13])=[CH:8][C:4]=1[C:5]([OH:7])=O.C(N(CC)CC)C.ClC(OCC(C)C)=O.[C:31]12([N:38]3[CH2:42][CH2:41][CH2:40][CH:39]3[CH2:43][NH2:44])[CH2:37][CH:34]([CH2:35][CH2:36]1)[CH2:33][CH2:32]2>O.CC(C)=O>[C:31]12([N:38]3[CH2:42][CH2:41][CH2:40][CH:39]3[CH2:43][NH:44][C:5](=[O:7])[C:4]3[CH:8]=[C:9]([S:12]([CH3:15])(=[O:14])=[O:13])[CH:10]=[CH:11][C:3]=3[O:2][CH3:1])[CH2:37][CH:34]([CH2:35][CH2:36]1)[CH2:33][CH2:32]2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 1708405-Mesyl-o-anisic acidHCID 201968811-Norbornyl-2-aminomethyl pyrrolidine

Product 1

HCID 57108672N-(1-norbornyl-2-pyrrolidylmethyl)-2-methoxy-5-methylsulphonyl benzamideYield 59%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

69 g of 2-methoxy-5-methylsulphonylbenzoic acid (0.30 mole), 360 ml of acetone, 120 ml of water and 30.3 g of triethylamine (0.30 mole) are placed in a 1 liter flask fitted with an agitator, thermometer, a condenser and a dropping funnel. The solution is chilled to 0° C., then 40.8 g of isobutyl chloroformate (0.30 mole) is added drop by drop. The mixture is agitated for 30 minutes at room temperature, then chilled to 0° C. again, and 58.2 g of 1-norbornyl-2-aminomethyl pyrrolidine (0.30 mole) is poured in drop by drop. The reaction mixture is agitated for 3 hours at room temperature then evaporated dry. The residue is dissolved in 500 ml of water and 80 ml of hydrochloric acid (density 1.18). The solution is filtered with acticarbone 3S and the filtrate is made alkaline with 120 ml of soda lye. A thick oil is decanted off, washed with 500 ml of water then dissolved hot, at about 60° C., in 90 ml of ethyl acetate. The product crystallises. The crystals are frozen, filtered and washed in water and dried in an oven at 60° C. 72 g of product is obtained (melting point 125° C.). This is re-crystallised in 150 ml of isopropanol to give 62 g (51%) of amide melting at 132° C.

Workup

  1. customfitted with an agitator
  2. temperaturechilled to 0° C. again
  3. stirringThe reaction mixture is agitated for 3 hours at room temperature
  4. customthen evaporated
  5. customdry
  6. dissolutionThe residue is dissolved in 500 ml of water
  7. filtrationThe solution is filtered with acticarbone 3S
  8. customA thick oil is decanted off
  9. washwashed with 500 ml of water
  10. dissolutionthen dissolved hot, at about 60° C., in 90 ml of ethyl acetate
  11. customThe product crystallises
  12. temperatureThe crystals are frozen
  13. filtrationfiltered
  14. washwashed in water
  15. customdried in an oven at 60° C

Sources & evidence

ORD record
ord-86e51fe92c4049949505360b00e72630
Source dataset
uspto-grants-1987_06
Patent number
US04673686

Reaction notes

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