Diethyl Ether → HCID 20393369, compound

HRID 1112503Notes

Reaction equation

HRID 1112503 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[N:6]([CH3:21])[C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:8]2[C:13]=1[CH:12]=[CH:11][C:10]([Cl:14])=[CH:9]2)=[O:4].[CH3:22][CH2:23][O:24]CC.[CH3:27]N(C)C=O>>[OH:24][CH2:23][CH2:22][CH2:1][N:2]([CH3:27])[C:3]([C:5]1[N:6]([CH3:21])[C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[C:8]2[C:13]=1[CH:12]=[CH:11][C:10]([Cl:14])=[CH:9]2)=[O:4]

Participants

4

Reactant 3

HCID 3283Diethyl EtherHCID 6228Dimethylformamide2×HCID 54545674HCID 54545674, compound

Product 1

HCID 20393369HCID 20393369, compound

Conditions

Temperature
100 °C

Procedure

A suspension of 30.0 g. of 5-chloro-2-methyl-3-phenylisoindole-1-carboxylic acid methylamide in 380 ml. of dimethylformamide is treated under an atmosphere of argon with 16.8 g. of potassium tert. butylate and the mixture is stirred in an ice-bath for 15 minutes. At 10°-15° C. there is then added a solution of 44.5 g. of (3-bromopropyl) [tetrahydropyranyl-(2)] ether in 30 ml. of dimethylformamide, the mixture is then stirred at 20°-25° C. for 30 minutes and subsequently heated to 100° C. for 30 minutes. After cooling, the solvent is removed by evaporation under reduced pressure and the residue partitioned between water and methylene chloride. The organic phase is washed with water, dried over sodium sulfate and evaporated to dryness. The residual oily tetrahydropyranyl derivative is dissolved in a mixture of 120 ml. of ethanol, 80 ml. of water and 20 ml. of concentrated hydrochloric acid and the solution is boiled at reflux for 3 hours. The mixture is then evaporated to dryness under reduced pressure and the residue dissolved in methylene chloride. The organic solution is washed with a saturated aqueous sodium chloride solution and dried over sodium sulfate. After concentration, the residue is purified by chromatography on 500 g. of silica gel using methylene chloride/ethyl acetate (2:1) for the elution, and there is obtained 5-chloro-2-methyl-3-phenylisoindole-1-carboxylic acid (3-hydroxypropyl)methylamide having a melting point of 85°-88° C. which can be used in the next step without further purification. An analytical sample is obtained by recrystallization from methylene chloride/pentane and has a melting point of 92°-94° C.

Workup

  1. additionA suspension of 30.0 g
  2. additionAt 10°-15° C. there is then added a solution of 44.5 g
  3. temperatureAfter cooling
  4. customthe solvent is removed by evaporation under reduced pressure
  5. customthe residue partitioned between water and methylene chloride
  6. washThe organic phase is washed with water
  7. dry with materialdried over sodium sulfate
  8. customevaporated to dryness
  9. dissolutionThe residual oily tetrahydropyranyl derivative is dissolved in a mixture of 120 ml
  10. temperatureat reflux for 3 hours
  11. customThe mixture is then evaporated to dryness under reduced pressure
  12. dissolutionthe residue dissolved in methylene chloride
  13. washThe organic solution is washed with a saturated aqueous sodium chloride solution
  14. dry with materialdried over sodium sulfate
  15. concentrationAfter concentration
  16. customthe residue is purified by chromatography on 500 g
  17. washfor the elution

Sources & evidence

ORD record
ord-afa779e686374d128dd3a082480aa3ee
Source dataset
uspto-grants-1978_10
Patent number
US04122265

Reaction notes

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