1-Bromo-3-chloropropane → 2-(3-Chloropropoxy)-1-methoxy-4-nitrobenzene

HRID 1593761Notes

Reaction equation

HRID 1593761 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:4]=1[OH:12].[OH-].[Na+].Br[CH2:16][CH2:17][CH2:18][Cl:19]>C(O)(C)C>[Cl:19][CH2:18][CH2:17][CH2:16][O:12][C:4]1[CH:5]=[C:6]([N+:9]([O-:11])=[O:10])[CH:7]=[CH:8][C:3]=1[O:2][CH3:1]

Participants

5

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 14798Sodium HydroxideHCID 694712-Methoxy-5-nitrophenol

Product 1

HCID 133001802-(3-Chloropropoxy)-1-methoxy-4-nitrobenzeneYield 81.8%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
75 °C

Procedure

2-methoxy-5-nitrophenol (50 g, 0.30 mol) was combined with 250 mL isopropyl alcohol. 1N sodium hydroxide solution, 310 mL (0.31 mol), was added to the mixture at such a rate that the temperature remained below 40° C. After the addition was completed, the mixture was stirred for at least 30 minutes. The reaction was then charged with 1-bromo-3-chloropropane (93.1 g, 0.59 mol) in a single portion. The mixture was heated to 75° C. and monitored periodically by high performance liquid chromatography (HPLC). After 8 hours, heating was discontinued and the reaction mixture was allowed to cool to ambient temperature overnight. The product gradually precipitated from the mixture as a light yellow/tan solid. Water, 200 mL, was added in a single portion and the resulting slurry was stirred for at least 30 minutes. The slurry was filtered and washed with water. The damp crude product was slurried in 650 mL methanol and heated to reflux until the solids had dissolved or mostly dissolved. The solution was allowed to cool gradually with stirring to ambient temperature over 3-5 hours or longer. The mixture was then cooled to 10-15° C. and held for at least 30 minutes. The solids were filtered and washed with cold methanol. The product was then dried in vacuo to give 60.3 g of 2-(3-chloropropoxy)-1-methoxy-4-nitrobenzene.

Workup

  1. customremained below 40° C
  2. additionAfter the addition
  3. temperatureheating
  4. temperatureto cool to ambient temperature overnight
  5. customThe product gradually precipitated from the mixture as a light yellow/tan solid
  6. additionWater, 200 mL, was added in a single portion
  7. stirringthe resulting slurry was stirred for at least 30 minutes
  8. filtrationThe slurry was filtered
  9. washwashed with water
  10. temperatureheated
  11. temperatureto reflux until the solids
  12. dissolutionhad dissolved
  13. dissolutionmostly dissolved
  14. temperatureto cool gradually
  15. stirringwith stirring to ambient temperature over 3-5 hours or longer
  16. temperatureThe mixture was then cooled to 10-15° C.
  17. waitheld for at least 30 minutes
  18. filtrationThe solids were filtered
  19. washwashed with cold methanol
  20. customThe product was then dried in vacuo

Sources & evidence

ORD record
ord-5706975e3a3349dc8beb51689fff7a73
Source dataset
uspto-grants-2007_11
Patent number
US07297795B2

Reaction notes

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