Diethyl Ether → HCID 45086344, compound

HRID 964326Notes

Reaction equation

HRID 964326 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10](=[O:12])[CH3:11])[N:5]=1)(=[O:3])[CH3:2].CCOCC.N(CCO)CCO>C1COCC1>[C:1]([C:4]1[N:5]=[C:6]([C@H:10]([CH3:11])[OH:12])[CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 8113DiethanolamineHCID 707902,6-Diacetylpyridine

Product 1

HCID 45086344HCID 45086344, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-18 °C

Procedure

(-)-DIP-Cl (about 70% in hexane, about 22 mmol) was evaporated under reduced pressure to remove hexane. The resulting oil was dissolved in THF (15 ml) and added over 5 minutes into the solution of 2,6-diacetylpyridine (Example 23, 1.0 g, 6.13 mmol) in THF (20 ml) which had been cooled to -18° C. with ice-salt bath. The resulting orange solution was stirred at -18° C. to room temperature for 24 hours. Ether (60 ml) was added. The solution was cooled to 0° C. and then (HOCH2 CH2)2NH (5 ml, 52 mmol) was added. The resulting suspension was stirred at 0° C. to room temperature for 6 hours and filtered through Celite. The filtrate was evaporated to dryness. The residue was taken into ether/hexane, and filtered again. This operation was repeated a few times until there was little solid left when the residue was treated with ether/hexane. The final residue was subjected to chromatography on silica gel column, eluted consecutively with hexane/AcOEt (8:1) hexane/AcOEt (1:4). The crude product obtained was subjected to chromatography on a silica gel column again, and eluted consecutively with hexane/AcOEt (8:1), hexane/AcOEt/Et3N (800:600;14), hexane/AcOEt (1;3). From hexane/AcOEt/Et3N (800:600;14) eluant, (S)-(-)-6-acetyl-a-methyl-2-pyridinemethanol was obtained. From hexane/AcOEt (1:3) eluant monitored by chiral GC column (fused silica capillary column, SUPLECO β-DEX# 120, 30 m×0.25 mm, 150° C.), (S,S)-(-)-α,α'-dimethyl-2,6-pyridinedimethanol pyridinedimethanol was obtained. Yield: 0.41 g (40%). EE: 98%, containing 0.5% meso-isomer. 1H-NMR (CDCl3): dH=7.68 (t, 3J(HH)=7.7 Hz, 1 H, H-gpy), 7.20 (d, 3 j(HH)=7.7 Hz, 2 H, H-bpy), 4.88 (q, 3J(HH)=6.6 Hz, 2 H, CH), 3.94 (s, broad, 2 H, OH), 1.49 (d, J(HH)=6.6 Hz, 6 H, CH3). 13C-NMR (CDCl3): dC=162.06 (C2,6), 137.64 (C4), 118.26 (C3,5), 69.18 (CHOH), 24.07 (CH3).

Workup

  1. customto remove hexane
  2. dissolutionThe resulting oil was dissolved in THF (15 ml)
  3. temperatureThe solution was cooled to 0° C.
  4. stirringThe resulting suspension was stirred at 0° C. to room temperature for 6 hours
  5. filtrationfiltered through Celite
  6. customThe filtrate was evaporated to dryness
  7. filtrationfiltered again
  8. waitleft when the residue
  9. additionwas treated with ether/hexane
  10. washeluted consecutively with hexane/AcOEt (8:1) hexane/AcOEt (1:4)
  11. customThe crude product obtained
  12. washeluted consecutively with hexane/AcOEt (8:1), hexane/AcOEt/Et3N (800:600;14), hexane/AcOEt (1;3)

Sources & evidence

ORD record
ord-ed1bde7ddeaa4e39930d5a63d8cdb06b
Source dataset
uspto-grants-1998_06
Patent number
US05767276

Reaction notes

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