반응 #58790

ord-ff95fa76aa7942059c0be08e6bf74b99

반응 조건

온도
0°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타A dry 500 mL, three-necked, round-bottomed flask was fitted with a magnetic stirring bar and a 60 mL pressure-equalizing addition funnel
  2. 2
    기타flushed with nitrogen gas
  3. 3
    workup.STIRRINGto stir at room temperature for 4 h (LC/MS
  4. 4
    온도cooled to 0° C.
  5. 5
    workup.STIRRINGwhile stirring
  6. 6
    기타White crystalline solid formed
  7. 7
    여과which was collected by filtration
  8. 8
    기타The crude compound was recrystallized from a mixture of ethanol and ethyl ether (50 mL: 150 mL.) Finally the white crystals
  9. 9
    세척were washed with 250 mL of ethyl acetate

실험 절차

A dry 500 mL, three-necked, round-bottomed flask was fitted with a magnetic stirring bar and a 60 mL pressure-equalizing addition funnel and flushed with nitrogen gas. The flask was charged with gabapentin (17.1 g, 0.1 mol) and benzyl alcohol (128 mL, 1.18 mol) and the mixture was cooled to 0° C. with an ice-water bath. Thionyl chloride (51.8 mL, 77.25 g, 0.65 mol) was added dropwise to the stirred solution over a period of 1 h. The reaction was monitored by LC/MS, with product and unreacted gabapentin hydrochloride being observed. After stirring at room temperature for 3.5 days the reaction mixture contained residual gabapentin hydrochloride (by LC/MS). Additional thionyl chloride (20 mL, 30 g, 0.25 mol) was added at 0° C., and the reaction mixture allowed to stir at room temperature for another 12 h (LC/MS shows traces of residual gabapentin hydrochloride). A final portion of thionyl chloride (10 mL, 15 g, 0.12 mol) was added at 0° C. and the reaction mixture allowed to stir at room temperature for 4 h (LC/MS showed no remaining gabapentin hydrochloride). The reaction mixture was then diluted with ethyl ether (200 mL) and cooled to 0° C. while stirring. White crystalline solid formed, which was collected by filtration. The crude compound was recrystallized from a mixture of ethanol and ethyl ether (50 mL: 150 mL.) Finally the white crystals were washed with 250 mL of ethyl acetate to give product (6) as a white solid (27 g, 91% yield). 1H NMR (CDCl3, 400 MHz.): δ 1.43-1.52 (m, 10H), 2.64 (s, 2H), 3.08 (d, 2H), 6.04 (br. s, 1H), 7.25-7.33 (m, 5H), 8.44 (br. s, 3H). MS (ESI) m/z 262.26 (M+H+).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07423169B2uspto-grants-2008_09