(R)-2-(tetrahydro-pyran-2-yloxy)-propionic acid methyl ester → (2R)-2-((tetrahydro-2H-pyran-2-yl)oxy)propan-1-ol

HRID 2098237ノート

反応式

HRID 2098237 の反応式
[H-].[H-].[H-].[H-].[Li+].[Al+3].C[O:8][C:9](=O)[C@H:10]([O:12][CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][O:14]1)[CH3:11]>CCOCC>[O:14]1[CH2:15][CH2:16][CH2:17][CH2:18][CH:13]1[O:12][C@H:10]([CH3:11])[CH2:9][OH:8]

参加物

4

反応物 2

HCID 11593565(R)-2-(tetrahydro-pyran-2-yloxy)-propionic acid methyl esterHCID 21226445Aluminium lithium hydride

生成物 1

HCID 9793900(2R)-2-((tetrahydro-2H-pyran-2-yl)oxy)propan-1-ol

試薬・触媒・溶媒 1

HCID 3283Diethyl Ether溶媒

実験手順

To a stirred solution of (R)-2-hydroxy-propionic acid methyl ester (10 g) and 3,4-dihydro-2H-pyran (15 mL) in DCM (400 mL) was added camphorsulfonic acid (50 mg) (exothermic reaction). The reaction mixture was stirred at ambient temperature for 2 hours, and washed with saturated bicarbonate solution (20 mL). The organic layer was dried, filtered and concentrated to obtain crude (R)-2-(tetrahydro-pyran-2-yloxy)-propionic acid methyl ester, which was used as is in the next step. To a stirred suspension of LAH (4 g) in anhydrous ether (400 mL) at 0-5° C. was added (R)-2-(tetrahydro-pyran-2-yloxy)-propionic acid methyl ester dropwise over 30 minute period. After completion of the addition, the cold bath was removed and the reaction mixture was stirred at room temperature for 2 hours. The resulting mixture was cooled to 0-5° C., and ethyl acetate was added dropwise to quench excess LAH, which was followed by the addition of saturated sodium sulfate solution and solid sodium sulfate. The resulting mixture was stirred at room temperature for 1 hour, the solid was filtered off, and the solid was washed with ether. The combined organic layer was dried over Na2SO4, filtered, concentrated and the residue was purified by column chromatography using a silica gel stationary phase (pre-treated with 0.1 triethylamine in hexanes) and hexanes in ethyl acetate to get (R)-2-(tetrahydro-pyran-2-yloxy)-propan-1-ol. 1H NMR (400 MHz, CDCl3): δ 4.51-4.75 (1H, m) 3.76-4.02 (2H, m) 3.42-3.62 (3H, m) 1.67-1.90 (2H, m) 1.46-1.63 (4 h, m) 1.10-1.24 (3H, m).

後処理

  1. additionAfter completion of the addition
  2. customthe cold bath was removed
  3. temperatureThe resulting mixture was cooled to 0-5° C.
  4. additionethyl acetate was added dropwise
  5. customto quench excess LAH, which
  6. additionwas followed by the addition of saturated sodium sulfate solution and solid sodium sulfate
  7. stirringThe resulting mixture was stirred at room temperature for 1 hour
  8. filtrationthe solid was filtered off
  9. washthe solid was washed with ether
  10. dry with materialThe combined organic layer was dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customthe residue was purified by column chromatography

出典と根拠

ORDレコード
ord-be3ff8993ff2448ba7a9c05d3418ffd5
出典データセット
uspto-grants-2013_05
特許番号
US08450354B2

反応ノート

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