Acetic Acid → HCID 117749009, compound

HRID 1504538Notes

Reaction equation

HRID 1504538 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:4][C:3]=1/[CH:16]=[CH:17]/[C:18]([O:20][CH2:21][CH3:22])=[O:19].[F:23][C:24]1[CH:25]=[C:26]([CH:30]2[CH2:34][CH2:33][C:32](=O)[CH2:31]2)[CH:27]=[CH:28][CH:29]=1.C(O)(=O)C.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>CCOC(C)=O.CCCCCCC.C(Cl)Cl.O1CCCC1.CO>[CH2:9]([S:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][CH:33]2[CH2:32][CH2:31][CH:30]([C:26]3[CH:27]=[CH:28][CH:29]=[C:24]([F:23])[CH:25]=3)[CH2:34]2)=[C:3](/[CH:16]=[CH:17]/[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:4]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

11

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 64521714HCID 64521714, compoundHCID 117740420(E)-Ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate

Product 1

HCID 117749009HCID 117749009, compoundYield 45.8%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×HCID 8900HeptaneSolvent

Procedure

A 40-mL vial was charged with (E)-ethyl 3-(2-amino-5-(benzylthio)phenyl)acrylate (1.2 g, 3.73 mmol) and 3-(3-fluorophenyl)cyclopentanone (665 mg, 3.73 mmol) then purged with nitrogen for 10 min. Methanol (16.0 ml), tetrahydrofuran (4.0 ml), and acetic acid (1.89 ml, 33.0 mmol) were sequentially introduced. Sodium cyanoborohydride (469 mg, 7.46 mmol) was then added in a single portion to the yellow reaction mixture. The vial was sealed with a PTFE line cap and the solution stirred vigorously at ambient temperature. After 16 h, the reaction mixture was heated to 50° C. After 22 h, the reaction mixture was allowed to cool to ambient temperature and carefully poured into a mixture of ice and a saturated aqueous solution of sodium bicarbonate. The mixture was stirred until, it reached ambient temperature then it was diluted with EtOAc (30 mL) and the layers were separated. The aqueous layer was further extracted with EtOAc (3×50 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate solution (100 mL) and brine (100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was then purified by flash column chromatography (50-g Biotage column, eluent: gradient, 20 to 70% EtOAc in heptane with CH2Cl2 as a 10% additive) to afford (E)-ethyl 3-(5-(benzylthio)-2-((3-(3-fluorophenyl)cyclopentyl)amino)phenyl)acrylate (812 mg, 1.707 mmol, 45.8% yield) as a yellow solid. m/z (ESI) 476.2 (M+H)+.

Workup

  1. customthen purged with nitrogen for 10 min
  2. customcap
  3. temperaturethe reaction mixture was heated to 50° C
  4. waitAfter 22 h
  5. temperatureto cool to ambient temperature
  6. additioncarefully poured into a mixture of ice
  7. stirringThe mixture was stirred until, it
  8. customreached ambient temperature
  9. customthe layers were separated
  10. extractionThe aqueous layer was further extracted with EtOAc (3×50 mL)
  11. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution (100 mL) and brine (100 mL)
  12. dry with materialdried over anhydrous magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was then purified by flash column chromatography (50-g Biotage column, eluent

Sources & evidence

ORD record
ord-58d071741e0a4bda8a6150248dff5ddd
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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