Water → 9-(3,4-Dimethoxy-benzyl)-2,3-dimethoxy-6,7,8,9-tetrahydro-5-thia-8-aza-benzocycloheptene

HRID 458799Notes

Reaction equation

HRID 458799 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][C:12]([NH:14][CH2:15][CH2:16][S:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([O:26][CH3:27])[CH:19]=2)=O)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].O=P(Cl)(Cl)Cl.[BH4-].[Na+].O>CC#N.C(Cl)Cl.CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][C:8]=1[O:9][CH3:10])[CH2:11][CH:12]1[C:23]2[CH:22]=[C:21]([O:24][CH3:25])[C:20]([O:26][CH3:27])=[CH:19][C:18]=2[S:17][CH2:16][CH2:15][NH:14]1

Participants

7

Reactant 4

HCID 962WaterHCID 24813Phosphorus oxychlorideHCID 4311764Sodium borohydrideHCID 184425752-(3,4-Dimethoxy-phenyl)-N-[2-(3,4-dimethoxy-phenylsulfanyl)-ethyl]-acetamide

Product 1

HCID 184425899-(3,4-Dimethoxy-benzyl)-2,3-dimethoxy-6,7,8,9-tetrahydro-5-thia-8-aza-benzocyclohepteneYield 30.4%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2-(3,4-dimethoxy-phenyl)-N-[2-(3,4-dimethoxy-phenylsulfanyl)-ethyl]-acetamide (4.0 g, 10.0 mmol) in dry CH3CN (21 ml), was added POCl3 (2.80 ml, 30.0 mmol). The resulting mixture was stirred at reflux for 3 h under nitrogen. After cooling, the reaction mixture was concentrated in vacuo and the residue was dissolved in MeOH (85 ml). The solution was cooled to 0° C. and NaBH4 (2.7 g, 69.0 mmol) was added portionwise, the resulting pale yellow suspension was stirred at RT for 16 h under nitrogen. The reaction mixture was poured into H2O and extracted three times with CH2Cl2. The combined organic phases were dried over anhydrous MgSO4, filtered and concentrated to give a crude oil. Flash chromatography (CH2Cl2/MeOH: 9/1) gave the title product (1.14 g, 27%) as a viscous brown oil.

Workup

  1. temperatureat reflux for 3 h under nitrogen
  2. temperatureAfter cooling
  3. concentrationthe reaction mixture was concentrated in vacuo
  4. dissolutionthe residue was dissolved in MeOH (85 ml)
  5. stirringthe resulting pale yellow suspension was stirred at RT for 16 h under nitrogen
  6. extractionextracted three times with CH2Cl2
  7. dry with materialThe combined organic phases were dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a crude oil

Sources & evidence

ORD record
ord-7679a0520a214ad8b47b212f5b098c19
Source dataset
uspto-grants-2007_03
Patent number
US07192950B2

Reaction notes

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