Hydrochloric Acid → 11-[4-(2-Piperidin-1-yl-ethoxy)-phenyl]-11,13-dihydro-12-oxa-benzo[3,4]cyclohepta[1,2-a]naphthalene-2,8-diolhydrochloride salt

HRID 916869Notes

Reaction equation

HRID 916869 reaction equation
C[O:2][C:3]1[CH:38]=[CH:37][C:6]2[C:7]3[C:8]([CH:19]([C:22]4[CH:36]=[CH:35][C:25]([O:26][CH2:27][CH2:28][N:29]5[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]5)=[CH:24][CH:23]=4)[O:20][CH2:21][C:5]=2[CH:4]=1)=[C:9]1[C:14](=[CH:15][CH:16]=3)[CH:13]=[C:12]([O:17]C)[CH:11]=[CH:10]1.C(S)C.[Na].O.[ClH:44]>CN(C=O)C.C(OCC)(=O)C>[ClH:44].[N:29]1([CH2:28][CH2:27][O:26][C:25]2[CH:24]=[CH:23][C:22]([CH:19]3[C:8]4=[C:9]5[C:14](=[CH:15][CH:16]=[C:7]4[C:6]4[CH:37]=[CH:38][C:3]([OH:2])=[CH:4][C:5]=4[CH2:21][O:20]3)[CH:13]=[C:12]([OH:17])[CH:11]=[CH:10]5)=[CH:36][CH:35]=2)[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 45051917Sodium ethanethiol2×HCID 589615391-{2-[4-(2,8-Dimethoxy-11,13-dihydro-12-oxa-benzo[3,4]cyclohepta[1,2-a]naphthalen-11-yl)-phenoxy]-ethyl}-piperidine

Product 1

HCID 13172660611-[4-(2-Piperidin-1-yl-ethoxy)-phenyl]-11,13-dihydro-12-oxa-benzo[3,4]cyclohepta[1,2-a]naphthalene-2,8-diolhydrochloride salt

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Dissolve 1-{2-[4-(2,8-dimethoxy-11,13-dihydro-12-oxa-benzo[3,4]cyclohepta[1,2-a]naphthalen-11-yl)-phenoxy]-ethyl}-piperidine (195 mg, 0.383 mmol) in DMF. Add sodium ethanethiol (306 mg, 3.65 mmol) and reflux. Reflux the reaction for 48 hours. Add more sodium ethanethiol (230 mg) and reflux for an additional 10 hours. Pour reaction onto ice and partion between water and ethyl acetate. Bring aqueous layer to a pH of about 1-2 using 6M HCl. Extract the aqueous layer three times with ethyl acetate. Combine extracts and wash with brine. Concentrate in vacuo and purify on a SCX column to yield 62 mg of free base title compound. Extract the aqueous layer again to retrieve more product. Combine the products and purify by precipitation from ether. Filter the solid and redissolve with methanol and 1M HCl. Concentrate in vacuo to yield 140 mg of the title compound. 1H NMR (d6-DMSO) δ 10.87 (s, 1H), 10.02 (s, 1H), 9.71 (s, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.46 (d, J=8.6 Hz, 1H), 7.24 (d, J=2.1 Hz, 1H), 7.15 (m, 1H), 6.83 (d, J=1.8 Hz, 2H), 6.7 (m, 4H), 6.58 (m, 3H), 4.50 (ab, Jab=12.5 Hz, 1H), 4.32 (ab, Jab=11.3 Hz, 1H), 4.24 (s, 2H), 3.32 (m, 4H), 2.90 (m, 2H).

Workup

  1. temperatureReflux
  2. customthe reaction for 48 hours
  3. temperaturereflux for an additional 10 hours
  4. additionPour
  5. extractionExtract the aqueous layer three times with ethyl acetate
  6. washCombine extracts and wash with brine
  7. concentrationConcentrate in vacuo
  8. custompurify on a SCX column

Sources & evidence

ORD record
ord-b8fc7616554a47289eb35eda53058dab
Source dataset
uspto-grants-2007_09
Patent number
US07271264B2

Reaction notes

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