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

HRID 1871043Notes

Reaction equation

HRID 1871043 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 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Method C A solution of 3-chloropropanol (142.47 g, 1.51 mol) in dichloromethane (1200ml) was cooled to -20° C. In a second vessel dichloromethane (1300 ml), methyl indole-3-carboxylate (240.0 g, 1.37 mol) and 1,4-diazabicyclo[2.2.2]octane (84.52 g 0.75 mol) 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 sulfonic 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 (1250 ml) was added and the mixture stirred for about 30 minutes. The organic layer was separated and washed once more with 10% sodium carbonate solution (1250 ml) and once with water (1250 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The concentrate was triturated with toluene (400 ml) and the mixture stirred at 0° C. for about 1 hour. The resulting solid was filtered, washed with toluene and dried in vacuo to give methyl 2-(3-chloropropoxy)-indole-3-carboxylate (245.5 g) as a white crystalline solid in 67% 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. stirringthe mixture stirred for about 30 minutes
  5. customThe organic layer was separated
  6. washwashed once more with 10% sodium carbonate solution (1250 ml) and once with water (1250 ml)
  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 toluene (400 ml)
  11. stirringthe mixture stirred at 0° C. for about 1 hour
  12. filtrationThe resulting solid was filtered
  13. washwashed with toluene
  14. customdried in vacuo

Sources & evidence

ORD record
ord-8bd9c2fb93fc439fb869d5a83ae2aa50
Source dataset
uspto-grants-2000_08
Patent number
US06100397

Reaction notes

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