Hydrochloric Acid → Ethyl 4-(2-fluorophenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxylate

HRID 2361239Notes

Reaction equation

HRID 2361239 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([C:11]1[C:19]2[C:14](=[CH:15][C:16]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[CH:17][CH:18]=2)[NH:13][CH:12]=1)[CH2:9][NH2:10].O=[CH:27][C:28]([O:30][CH2:31][CH3:32])=[O:29].C1(C)C=CC=CC=1.Cl>O1CCOCC1.C(OCC)(=O)C.CCCCCC>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:11]2[C:19]3[C:14](=[CH:15][C:16]([N:20]4[CH2:21][CH2:22][O:23][CH2:24][CH2:25]4)=[CH:17][CH:18]=3)[NH:13][C:12]=2[C:27]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[N:10][CH:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 70211Ethyl oxoacetateHCID 679947912-(2-Fluorophenyl)-2-(6-morpholino-1H-indol-3-yl)ethanamine

Product 1

HCID 67994836Ethyl 4-(2-fluorophenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxylateYield 41.6%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a solution of 2-(2-fluorophenyl)-2-(6-morpholino-1H-indol-3-yl)ethanamine (0.181 g, 0.533 mmol) and ethyl 2-oxoacetate in toluene (50%) (0.233 mL, 1.173 mmol) in 1,4-dioxane (18 mL) at room temperature was added hydrogen chloride (4 N in 1,4-dioxane) (0.267 mL, 1.067 mmol). The solution turned heterogeneous and it was stirred at room temperature for 16 hr. The volatiles were removed under vacuum. The residue was diluted with water (20 mL), basified with saturated NaHCO3 solution to pH 10, and extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (25 ml), dried over anhydrous MgSO4, and concentrated to dryness under vacuum. To the residue were added toluene (10 mL) and 10% Pd/C (0.3 g), and the mixture was heated at 140° C. under an ambient atmosphere for 4.5 hr. The solid phase was removed by suction filtration. The filtrate was diluted with ethyl acetate (100 ml), washed with brine (25 ml), and dried over anhydrous MgSO4. The desired product (94 mg, 0.222 mmol, 41.6% yield) was isolated with ISCO (24 g silica gel, 30-60% ethyl acetate/hexane) as a tan solid.

Workup

  1. customThe volatiles were removed under vacuum
  2. additionThe residue was diluted with water (20 mL)
  3. extractionextracted with ethyl acetate (3×30 mL)
  4. extractionThe combined extract
  5. washwas washed with brine (25 ml)
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentrated to dryness under vacuum
  8. additionTo the residue were added toluene (10 mL) and 10% Pd/C (0.3 g)
  9. temperaturethe mixture was heated at 140° C. under an ambient atmosphere for 4.5 hr
  10. customThe solid phase was removed by suction filtration
  11. additionThe filtrate was diluted with ethyl acetate (100 ml)
  12. washwashed with brine (25 ml)
  13. dry with materialdried over anhydrous MgSO4

Sources & evidence

ORD record
ord-c76f8914e16744948ae4bd9e2cf6b024
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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