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

HRID 896866ノート

反応式

HRID 896866 の反応式
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

参加物

4

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

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]+.

後処理

  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]+

出典と根拠

ORDレコード
ord-e281bda4051545c79107b43b76b3b13d
出典データセット
uspto-grants-2005_07
特許番号
US06919371B2

反応ノート

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