Hydrochloric Acid → 7-chloro-9-(phenylsulfonyl)-2,3,4,5-tetrahydro-1H-benzofuro[2,3-d]azepine hydrochloride

HRID 2179432Notes

Reaction equation

HRID 2179432 reaction equation
[Cl:1][C:2]1[C:7]2[O:8][C:9]3[CH2:10][CH2:11][N:12](C(OCC)=O)[CH2:13][CH2:14][C:15]=3[C:6]=2[CH:5]=[C:4]([S:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH:3]=1.[OH-].[K+].Cl>C(O)CO.COCCOC.O.CO>[ClH:1].[Cl:1][C:2]1[C:7]2[O:8][C:9]3[CH2:10][CH2:11][NH:12][CH2:13][CH2:14][C:15]=3[C:6]=2[CH:5]=[C:4]([S:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH:3]=1

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 68109708ethyl 7-chloro-9-(phenylsulfonyl)-4,5-dihydro-1H-benzofuro[2,3-d]azepine-3(2H)-carboxylate

Product 1

HCID 681095877-chloro-9-(phenylsulfonyl)-2,3,4,5-tetrahydro-1H-benzofuro[2,3-d]azepine hydrochlorideYield 31.4%

Reagents, catalysts & solvents 4

HCID 174Ethylene GlycolSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

The product of step E (35 mg, 0.08 mmol) was dissolved in a mixture of ethylene glycol (0.5 mL) and DME (0.5 mL) then treated with 20% KOH solution (0.5 mL). The reaction mixture was heated to 100° C. for 36 h. After cooling to ambient temperature, the reaction mixture was diluted with water (5 mL) and extracted with dichloromethane (3×20 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by semi-preparative HPLC to give the free base which was treated directly with 1.25 M HCl in methanol solution. Concentration in vacuo afforded 7-chloro-9-(phenylsulfonyl)-2,3,4,5-tetrahydro-1H-benzofuro[2,3-d]azepine hydrochloride (5 mg, 15%, AUC HPLC>99%) as a white solid: 1H NMR (CD3OD, 300 MHz) δ 8.18 (d, J=2.0 Hz, 1H), 8.00 (d, J=7.4 Hz, 2H), 7.90 (d, J=1.7 Hz, 1H), 7.68-7.52 (m, 3H), 3.60-3.51 (m, 4H), 3.42-3.35 (m, 2H), 3.23-3.15 (m, 2H); APCI MS m/z 362 [M+H]+.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. extractionextracted with dichloromethane (3×20 mL)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by semi-preparative HPLC
  8. customto give the free base which
  9. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-3b96fb67846a4c88ac2dbadd84ed3e85
Source dataset
uspto-grants-2015_06
Patent number
US09067949B2

Reaction notes

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