Hydrochloric Acid → HCID 22503716, compound

HRID 2186688Notes

Reaction equation

HRID 2186688 reaction equation
[OH-:1].[K+].C([N:11]1[CH2:24][CH2:23][C:22]2[C:21]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[N:15]([CH2:25][CH2:26][C:27]([O:29]CC)=[O:28])[C:14]=2[CH2:13][CH2:12]1)(=O)C1C=CC=CC=1.Cl.[OH2:33]>C1COCC1>[C:26]([OH:33])(=[O:1])[C:27]([OH:29])=[O:28].[CH:20]1[C:21]2[C:22]3[CH2:23][CH2:24][NH:11][CH2:12][CH2:13][C:14]=3[N:15]3[C:16]=2[C:17]([C:27](=[O:28])[CH2:26][CH2:25]3)=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14797Potassium HydroxideHCID 22503757HCID 22503757, compound

Product 1

HCID 22503716HCID 22503716, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A solution of potassium hydroxide (0.80 g, 14.3 mmol) in H2O (20 mL) was added to a solution of ethyl 3-(3-benzoyl-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)propanoate (4.25 g, 10.9 mmol) in THF (30 mL). The reaction mixture was heated at 60° C. for 1 h, then cooled to room temperature, acidified with 10% aqueous HCl, and extracted with EtOAc. The combined organic extracts were washed with saturated aqueous NaCl, dried over Na2SO4, decanted, and concentrated under reduced pressure to give 3.73 g of crude acid. The crude acid (2.00 g, 5.52 mmol) was then added to neat PPA (18.6 g) stirring at 100° C. under N2. After 1.5 h, the reaction was cooled to room temperature, quenched with ice and 10% aqueous NaOH, and then extracted with EtOAc. The combined organic extracts were washed with saturated aqueous NaCl, dried over Na2SO4, decanted, and concentrated under reduced pressure. The crude product was purified by silica gel chromatography with EtOAc/hexanes (gradient 1:1 to 2:1) to give 0.81 g (43%) of the title compound as a yellow solid (mp 177.5-181° C.). 1H NMR (d-DMSO) δ 7.75, 7.46, 7.09, 4.45-4.24, 3.93, 3.61, 3.34, 3.17, 3.11-2.80; IR (drift) 1676, 1628, 1587, 1493, 1483, 1466, 1428, 1357, 1324, 1295, 1276, 1266, 1191, 754, 706 cm1.

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with EtOAc
  3. washThe combined organic extracts were washed with saturated aqueous NaCl
  4. dry with materialdried over Na2SO4
  5. customdecanted
  6. concentrationconcentrated under reduced pressure
  7. customto give 3.73 g of crude acid
  8. temperaturethe reaction was cooled to room temperature
  9. customquenched with ice and 10% aqueous NaOH
  10. extractionextracted with EtOAc
  11. washThe combined organic extracts were washed with saturated aqueous NaCl
  12. dry with materialdried over Na2SO4
  13. customdecanted
  14. concentrationconcentrated under reduced pressure
  15. customThe crude product was purified by silica gel chromatography with EtOAc/hexanes (gradient 1:1 to 2:1)

Sources & evidence

ORD record
ord-552a3af5c08f4797a7e8d9ba1903a2fc
Source dataset
uspto-grants-2002_06
Patent number
US06407092B1

Reaction notes

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