Methyl Chloride → HCID 70454110, compound

HRID 1381224Notes

Reaction equation

HRID 1381224 reaction equation
Cl.[Cl:2][C:3]1[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:4]=1[O:5][C@@H:6]1[CH2:10][N:9](CC2C=CC=CC=2)[CH2:8][C@H:7]1[OH:18].CCl.[CH2:26]([O:33][C:34](Cl)=[O:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>C(Cl)Cl>[Cl:2][C:3]1[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:4]=1[O:5][C@@H:6]1[CH2:10][N:9]([C:34]([O:33][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:35])[CH2:8][C@H:7]1[OH:18]

Participants

5

Reactant 3

HCID 6327Methyl ChlorideHCID 10387Benzyl chloroformateHCID 70454135HCID 70454135, compound

Product 1

HCID 70454110HCID 70454110, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 8.5 g (0.023 mole) of trans-4-(2,3-dichlorophenoxy)-1-phenylmethyl-3-pyrrolidinol hydrochloride and 100 liters of methyl chloride was cooled and treated dropwise with a solution of 23 g (0.125 mole) of benzylchloroformate in 100 ml of methylene chloride. The mixture was stirred at ambient temperature for 48 hr and then washed successively with water, 2N hydrochloric acid, 5% sodium hydroxide and water. The methylene chloride layer was dried over anhydrous sodium sulfate and then subjected to vacuum distillation at 100°/1.0 mm. to remove the methylene chloride, excess benzylchloroformate and benzyl chloride. An NMR analysis of the pot residue indicated only the oxygen was substituted. An additional 25 ml. of benzylchloroformate and 100 ml. of methylene chloride was added to the residue and the solution stirred at ambient temperature for 48 hr. The mixture was purified as above to give 14.6 g. of residue which was chromatographed on 300 g. of silica gel. The chromatography gave 5.6 g. of the disubstituted compound (See Example 20) and 1.0 g. of the titled compound as a white solid, m.p. 130°-2° C. (recrystallized from benzene).

Workup

  1. temperaturewas cooled
  2. washwashed successively with water, 2N hydrochloric acid, 5% sodium hydroxide and water
  3. dry with materialThe methylene chloride layer was dried over anhydrous sodium sulfate
  4. distillationsubjected to vacuum distillation at 100°/1.0 mm
  5. customto remove the methylene chloride, excess benzylchloroformate and benzyl chloride
  6. additionof methylene chloride was added to the residue
  7. stirringthe solution stirred at ambient temperature for 48 hr
  8. customThe mixture was purified as above
  9. customto give 14.6 g
  10. customof residue which was chromatographed on 300 g
  11. customThe chromatography gave 5.6 g
  12. customof the titled compound as a white solid, m.p. 130°-2° C. (recrystallized from benzene)

Sources & evidence

ORD record
ord-84b19462ae71480d9917528e07e3990f
Source dataset
uspto-grants-1986_04
Patent number
US04585785

Reaction notes

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