Methanesulfonic Acid → Methyl 2-(3-chloropropoxy)indole-3-carboxylate

HRID 1871041Notes

Reaction equation

HRID 1871041 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][OH:5].[NH:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([C:15]([O:17][CH3:18])=[O:16])=[CH:7]1.N12CCN(CC1)CC2.ClN1C(=O)CCC1=O.CS(O)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:7]1[NH:6][C:14]2[C:9]([C:8]=1[C:15]([O:17][CH3:18])=[O:16])=[CH:10][CH:11]=[CH:12][CH:13]=2

Participants

8

Reactant 6

HCID 6395Methanesulfonic AcidHCID 9237DabcoHCID 10340Sodium CarbonateHCID 123133-Chloro-1-propanolHCID 31398ChlorosuccinimideHCID 589098Methyl indole-3-carboxylate

Product 1

HCID 9816818Methyl 2-(3-chloropropoxy)indole-3-carboxylateYield 55.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Method B A solution of 3-chloropropanol (142.47 g, 1.51 mole) in dichloromethane (1200 ml) was cooled to -20° C. In a second vessel dichloromethane (1300 ml), methyl indole-3-carboxylate (240.0 g, 1.37 mole) and 1,4-diazabicyclo[2.2.2]octane (84.52 g 0.75 mole) were cooled to 0° C. N-Chlorosuccinimide (201.22 g 1.51 mole) was added to the second vessel and stirred at 0° C. for 10 minutes. In the meantime methane sulphonic acid (10.56 ml) was added to the first vessel. The solution in the second vessel was added to the first vessel keeping the temperature below about 0° C., and the resulting mixture stirred for a further 2.5 hours at -5 to 0° C. 10% Sodium carbonate solution (2500 ml) was added and stirred. The organic layer was separated and washed twice with 10% sodium carbonate solution (2500 ml each wash). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The concentrate was triturated with ethyl acetate (120 ml) and the mixture stirred at 0° C. for about 1 hour. The resulting solid was filtered, washed a small quantity of ethyl acetate and dried under vacuum to give methyl 2-(3-chloropropoxy)-indole-3-carboxylate (202.5 g) as a white crystalline solid in 55% yield.

Workup

  1. additionThe solution in the second vessel was added to the first vessel
  2. customthe temperature below about 0° C.
  3. stirringthe resulting mixture stirred for a further 2.5 hours at -5 to 0° C
  4. stirringstirred
  5. customThe organic layer was separated
  6. washwashed twice with 10% sodium carbonate solution (2500 ml each wash)
  7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe concentrate was triturated with ethyl acetate (120 ml)
  11. stirringthe mixture stirred at 0° C. for about 1 hour
  12. filtrationThe resulting solid was filtered
  13. washwashed a small quantity of ethyl acetate
  14. customdried under vacuum

Sources & evidence

ORD record
ord-21b2c9d8bb164ff8821fa27aadb112f0
Source dataset
uspto-grants-2000_08
Patent number
US06100397

Reaction notes

Loading…