Dichloromethane → HCID 20517541, compound

HRID 2198884Notes

Reaction equation

HRID 2198884 reaction equation
Br[CH:2]([CH3:6])[C:3](Br)=[O:4].[CH3:7][O:8][C:9]1[C:10](C)(CNC)[CH:11]([CH2:15][OH:16])[CH:12]=[CH:13][CH:14]=1.[CH2:21]([N:23](CC)[CH2:24]C)C.Cl[CH2:29]Cl>>[CH3:7][O:8][C:9]1[CH:10]=[C:11]([C:15]2([CH3:29])[CH2:21][N:23]([CH3:24])[C:3](=[O:4])[CH:2]([CH3:6])[O:16]2)[CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 4

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 79047Propanoyl bromide, 2-bromo-HCID 86738640HCID 86738640, compound

Product 1

HCID 20517541HCID 20517541, compound

Conditions

Temperature
85 °C

Procedure

2-Bromopropionylbromide (28.7 g, 0.13 mole) in dichloromethane (100 ml) was added dropwise with stirring to a solution of (3-methoxy)-2-methyl-2-[(methylamino)methyl]benzene methanol (25.9 g, 0.13 mol) and triethylamine (13.5 g) in dichloromethane (200 ml) keeping the temperature of the reaction between 10°-15° C. by ice-cooling. After 2 hours the reaction was washed with water, dilute hydrochloric acid and brine, dried (MgSO4) and evaporated to an oil (46.9 g). The last traces of dichloromethane were removed from the oil by evaporation with toluene. The oil was dissolved in dry toluene (200 ml) and added dropwise to a stirred suspension of sodium hydride (9.6 g, 0.2 mole of a 50% dispersion in oil pre-washed with ether) in dry dimethylformamide (200 ml) under nitrogen. The exothermic reaction which took place was kept at 35° C. by adjusting the rate of addition. When the addition was completed the reaction mixture was heated to 85° C. for 20 min. The reaction mixture was cooled and cautiously added to ice water (300 ml). The mixture was extracted with toluene and the organic extracts washed with dilute hydrochloric acid then brine. After drying (MgSO4) the solvent was removed to leave an oil which was distilled affording the title compound (25.8 g) as a colourless oil, bp 148°-149° at 0.7 mbar. Glc showed that the product was a mixture of diastereoisomers containing isomer A (apparently 2R*6R* configuration) 65% and isomer B (apparently 2R*6S* configuration) 35% by glc.

Workup

  1. customthe temperature of the reaction between 10°-15° C. by ice-
  2. temperaturecooling
  3. washAfter 2 hours the reaction was washed with water, dilute hydrochloric acid and brine
  4. dry with materialdried (MgSO4)
  5. customevaporated to an oil (46.9 g)
  6. customThe last traces of dichloromethane were removed from the oil by evaporation with toluene
  7. dissolutionThe oil was dissolved in dry toluene (200 ml)
  8. additionadded dropwise to a stirred suspension of sodium hydride (9.6 g, 0.2 mole of a 50% dispersion in oil
  9. washpre-washed with ether) in dry dimethylformamide (200 ml) under nitrogen
  10. customThe exothermic reaction which
  11. customwas kept at 35° C.
  12. additionthe rate of addition
  13. additionWhen the addition
  14. temperatureThe reaction mixture was cooled
  15. extractionThe mixture was extracted with toluene
  16. washthe organic extracts washed with dilute hydrochloric acid
  17. dry with materialAfter drying (MgSO4) the solvent
  18. customwas removed
  19. customto leave an oil which
  20. distillationwas distilled

Sources & evidence

ORD record
ord-b5a75e27d27c4d279dfa755f5fac8e0c
Source dataset
uspto-grants-1982_11
Patent number
US04360519

Reaction notes

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