Edetate Sodium → 3-Cyclopropylmethyl-8-methoxy-1,2,4,5-tetrahydro-3H-benz[e]indole

HRID 26398

Reaction equation

HRID 26398 reaction equation
[CH3:1][N:2]1[C:10]2[CH2:9][CH2:8][C:7]3[CH:11]=[CH:12][CH:13]=[CH:14][C:6]=3[C:5]=2[CH2:4][CH2:3]1.[CH:15]([Mg]Cl)([CH3:17])[CH3:16].BrC(Cl)C.[Na+].[Na+].[Na+].[Na+].C(N(CC([O-])=O)CC([O-])=O)CN(CC([O-])=O)C[C:32]([O-])=[O:33]>O1CCCC1>[CH:15]1([CH2:1][N:2]2[C:10]3[CH2:9][CH2:8][C:7]4[CH:11]=[CH:12][C:13]([O:33][CH3:32])=[CH:14][C:6]=4[C:5]=3[CH2:4][CH2:3]2)[CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 6144Edetate SodiumHCID 116541-Bromo-1-chloroethaneHCID 233308163-Methyl-1,2,4,5-tetrahydrobenzo[e]indoleHCID 178418918HCID 178418918, compound

Product 1

HCID 233307813-Cyclopropylmethyl-8-methoxy-1,2,4,5-tetrahydro-3H-benz[e]indole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

This compound was prepared according to the procedure described by Evans, et al., J. Org. Chem. 35, 4122 (1970) for the synthesis of 3-methyl-1,2,4,5-tetrahydro-3H-benz[e]indole as follows. Into a dry, nitrogen filled, one liter 3-neck flask fitted with reflux condenser, serum cap, dropping funnel and magnetic stirrer, was added a solution of 38.55 g (167.9 mmol) XIIa in dry tetrahydrofuran (THF) (50 ml) which was placed under a slow stream of nitrogen. A 2.20 M solution of isopropyl magnesium chloride in THF (96.1 ml, 211.7 mmol) was added slowly via a syringe at such a rate as to maintain gently reflux. After the addition (15 min), 30.72 g (214.2 mmol) of bromochloroethan was added to the warm reaction mixture at a rate sufficient to maintain gentle refluxing. After the addition of the alkylhalide, an additional 52.3 ml (115 mmol) of the Grignard reagent was added to the reaction again at a controlled rate. The reaction mixture was cooled in an ice-bath and 270 ml of 1 M aqueous solution of ethylenediaminetetraacetic acid tetrasodium salt was added slowly (with stirring) and then 600 ml of a 1:1 etherbenzene was added. The organic layer was separated and the aqueous phase was extracted with ether. The combined extracts were washed with water (2×100 ml) and dried (MgSO4). Removal of the solvent by evaporation gave 43.0 g (99%) of XIIIa as a pale yellow oxygen-sensitive oil; IR (neat), 1635 cm-1 (C=C--N).

Workup

  1. customThis compound was prepared
  2. additionInto a dry, nitrogen filled
  3. customone liter 3-neck flask fitted
  4. temperaturewith reflux condenser
  5. customserum cap
  6. temperatureto maintain gently
  7. temperaturereflux
  8. additionwas added to the warm reaction mixture at a rate sufficient
  9. temperatureto maintain gentle refluxing
  10. temperatureThe reaction mixture was cooled in an ice-bath
  11. addition600 ml of a 1:1 etherbenzene was added
  12. customThe organic layer was separated
  13. extractionthe aqueous phase was extracted with ether
  14. washThe combined extracts were washed with water (2×100 ml)
  15. dry with materialdried (MgSO4)
  16. customRemoval of the solvent
  17. customby evaporation

Sources & evidence

ORD record
ord-5f449708e7324f7dac99b5b54236f067
Source dataset
uspto-grants-1979_04
Patent number
US04150032

Linked notes

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