Sodium hydride → HCID 20368341, compound

HRID 616635Notes

Reaction equation

HRID 616635 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:11]=3[S:10][CH:9]=2)=[CH:4][CH:3]=1.Cl.Cl[CH2:21][CH2:22][N:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1.[H-].[Na+]>CN(C)C=O>[N:23]1([CH2:22][CH2:21][O:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[C:12]4[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:11]=4[S:10][CH:9]=3)=[CH:6][CH:7]=2)[CH2:27][CH2:26][CH2:25][CH2:24]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 816681-(2-Chloroethyl)pyrrolidine hydrochlorideHCID 22348372HCID 22348372, compound

Product 1

HCID 20368341HCID 20368341, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To 80 ml. of N,N-dimethylformamide (DMF) were added 10.0 grams (0.039 mole) of 3-(4-hydroxyphenyl)-6-methoxybenzothiophene. The mixture was cooled to 0° C., and 6.6 grams (0.039 mole) of N-(2-chloroethyl)pyrrolidine hydrochloride were added followed by 2.81 grams (0.117 mole) of sodium hydride added in small portions. Effervescence developed, and, when the effervescence had ceased, the mixture was heated at 95° C. for 14 hours. To the mixture then were added 10 ml. of ethanol, and the solvents of the resulting mixture then were evaporated. The resulting residue was dissolved in a mixture of water and ethyl acetate. The ethyl acetate layer was separated from the aqueous layer and was washed with 25 ml. of sodium chloride solution. The ethyl acetate solution then was extracted twice with 40 ml. of 1N hydrochloric acid. The acid layer was separated and rendered alkaline by addition of 50 ml. of 2N sodium hydroxide. The alkaline mixture then was extracted with 250 ml. of ethyl acetate. The ethyl acetate layer was separated, dried over magnesium sulfate, and evaporated to give 3-[4-(2-pyrrolidinoethoxy)phenyl]-6-methoxybenzothiophene as an oil. The oil was dissolved in methanol and treated with excess methanolic hydrochloric acid. The mixture was evaporated, and the solid residue was recrystallized from methanol to give 11.6 grams (76 percent) of the hydrochloride salt of 3-[4-(2-pyrrolidinoethoxy)phenyl]-6-methoxybenzothiophene, m.p. 200°-202° C.

Workup

  1. additionadded in small portions
  2. temperaturethe mixture was heated at 95° C. for 14 hours
  3. additionTo the mixture then were added 10 ml
  4. customof ethanol, and the solvents of the resulting mixture then were evaporated
  5. dissolutionThe resulting residue was dissolved in a mixture of water and ethyl acetate
  6. customThe ethyl acetate layer was separated from the aqueous layer
  7. washwas washed with 25 ml
  8. extractionThe ethyl acetate solution then was extracted twice with 40 ml
  9. customThe acid layer was separated
  10. additionby addition of 50 ml
  11. extractionThe alkaline mixture then was extracted with 250 ml
  12. customThe ethyl acetate layer was separated
  13. dry with materialdried over magnesium sulfate
  14. customevaporated

Sources & evidence

ORD record
ord-54a3324f4fc24157b11dafc1b4a6c24b
Source dataset
uspto-grants-1978_02
Patent number
US04075227

Reaction notes

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