(2R)-N-[(2S)-2-hydroxy-3-phenoxypropyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide → HCID 10203547, compound

HRID 47679Notes

Reaction equation

HRID 47679 reaction equation
[OH:1][C@H:2]([CH2:18][O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:3][NH:4][C:5]([C@H:7]1[CH2:16][CH2:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([I:17])[CH:13]=2)[O:8]1)=O.B.CSC>C1COCC1>[I:17][C:12]1[CH:13]=[C:14]2[C:9](=[CH:10][CH:11]=1)[O:8][C@@H:7]([CH2:5][NH:4][CH2:3][C@H:2]([OH:1])[CH2:18][O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:16][CH2:15]2

Participants

4

Reactant 2

HCID 10161252(2R)-N-[(2S)-2-hydroxy-3-phenoxypropyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamideHCID 12423031(Dimethyl sulfide)trihydroboron

Product 1

HCID 10203547HCID 10203547, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution containing (2R)-N-[(2S)-2-hydroxy-3-phenoxypropyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide (Example 79, 9.204 mmol, 1 eq.) in THF (140 mL) at room temperature was slowly added borane-methyl sulfide complex (2 M in THF, 46.07 mmol, 5.0 eq.). After completion of addition, reaction solution was heated to reflux, maintained at that temperature for 2 hours, and then cooled to room temperature. The resulting solution was quenched with EtOH (5 mL) dropwise, then with 2 M HCl (20 mL) slowly. The resulting mixture was heated at reflux for 1 hour and was then allowed to cool to room temperature. This solution was basified with 1 N NaOH and extracted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resulting residue was dissolved in MeOH and EtOAc and filtered. The filtrate was concentrated and dried in vacuo to afford the product as a white solid in 99% yield. MH+=440.2, retention time (LC-MS)=2.24 min.

Workup

  1. additionAfter completion of addition, reaction solution
  2. temperaturewas heated
  3. temperatureto reflux
  4. temperaturemaintained at that temperature for 2 hours
  5. customThe resulting solution was quenched with EtOH (5 mL) dropwise
  6. temperatureThe resulting mixture was heated
  7. temperatureat reflux for 1 hour
  8. temperatureto cool to room temperature
  9. extractionextracted with ethyl acetate
  10. extractionThe organic extract
  11. washwas washed with brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. concentrationconcentrated in vacuo
  14. dissolutionThe resulting residue was dissolved in MeOH
  15. filtrationEtOAc and filtered
  16. concentrationThe filtrate was concentrated
  17. customdried in vacuo

Sources & evidence

ORD record
ord-b4881a3f3ecf4677b6b76fe894ab6c8b
Source dataset
uspto-grants-2004_03
Patent number
US06699860B2

Reaction notes

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