(Dimethyl sulfide)trihydroboron → (1R)-2-({[(2R)-6-iodo-3,4-dihydro-2H-chromen-2-yl]methyl}amino)-1-(3-pyridinyl)ethanol

HRID 896866Notes

Reaction equation

HRID 896866 reaction equation
B.CSC.[OH:5][C@H:6]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)[CH2:7][NH:8][C:9]([C@H:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([I:21])[CH:17]=2)[O:12]1)=O>O1CCCC1>[I:21][C:16]1[CH:17]=[C:18]2[C:13](=[CH:14][CH:15]=1)[O:12][C@@H:11]([CH2:9][NH:8][CH2:7][C@@H:6]([C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1)[OH:5])[CH2:20][CH2:19]2

Participants

4

Reactant 2

HCID 12423031(Dimethyl sulfide)trihydroboronHCID 59118145(2R)-N-[(2R)-2-hydroxy-2-(3-pyridinyl)ethyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide

Product 1

HCID 59118135(1R)-2-({[(2R)-6-iodo-3,4-dihydro-2H-chromen-2-yl]methyl}amino)-1-(3-pyridinyl)ethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Borane-dimethylsulfide complex (2.0 M in tetrahydrofuran, 46 mL, 92 mmol) was added dropwise (20 minutes) to a cooled (0° C.) and stirred solution of (2R)-N-[(2R)-2-hydroxy-2-(3-pyridinyl)ethyl]-6-iodo-3,4-dihydro-2H-chromene-2-carboxamide (Example 35, Method A, 7.75 g, 18.3 mmol) in tetrahydrofuran (300 mL). The solution was warmed to reflux for 1 hour and then cooled to room temperature. The reaction was quenched with addition of methanol (12 mL) and 2 M hydrochloric acid (95 mL), and then the resulting solution was heated at reflux for 1 hour. The reaction was cooled to room temperature and then the solution was adjusted to pH 9 using 1 M aqueous sodium hydroxide. The mixture was diluted with brine (500 mL) and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×200 mL) and then the combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. Flash chromatography of the residue over silica gel using 30-50% ethyl acetate/hexane afforded product (6.32 g, 84%) as a waxy yellow solid: 1H NMR (acetone-d6, δ): 8.59 (d, J=1.9 Hz, 1 H), 8.44 (dd, J=5.0, 1.5 Hz, 1 H), 7.77 (ddd, J=8.0, 1.8, 1.8 Hz, 1 H), 7.25-7.39 (m, 3 H), 6.56 (d, J=8.4 Hz, 1 H), 4.80 (dd, J=8.4, 4.0 Hz, 1 H), 4.08-4.18 (m, 1 H), 2.67-3.00 (m, 10 H), 1.67-1.82 (m, 1 H); mass spectroscopy gave m/z=410.9 [M+H]+.

Workup

  1. temperatureThe solution was warmed
  2. temperatureto reflux for 1 hour
  3. temperaturecooled to room temperature
  4. customThe reaction was quenched with addition of methanol (12 mL) and 2 M hydrochloric acid (95 mL)
  5. temperaturethe resulting solution was heated
  6. temperatureat reflux for 1 hour
  7. temperatureThe reaction was cooled to room temperature
  8. additionThe mixture was diluted with brine (500 mL)
  9. customthe layers were separated
  10. extractionThe aqueous layer was extracted with ethyl acetate (2×200 mL)
  11. washthe combined organic extracts were washed with brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. concentrationconcentrated in vacuo
  14. custommass spectroscopy gave m/z=410.9 [M+H]+

Sources & evidence

ORD record
ord-e281bda4051545c79107b43b76b3b13d
Source dataset
uspto-grants-2005_07
Patent number
US06919371B2

Reaction notes

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