Hydrochloric Acid → (9S,10S)-2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid

HRID 258318

반응식

HRID 258318 반응식
[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[CH:12]3[CH2:16][C:5]([C:17]([OH:19])=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1.C[C@H](NC)[C@@H](O)C1C=CC=CC=1.O.Cl>C(OCC)(=O)C.CO.C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[C@H:12]3[CH2:16][C@:5]([C:17]([OH:19])=[O:18])([C:6]4[C:11]3=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:4]=2[CH:3]=1

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 7028PseudoephedrineHCID 196986472-Chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid

생성물 1

HCID 67637562(9S,10S)-2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid수율 81%

시약·촉매·용매 3

HCID 887Methanol용매HCID 6212Chloroform용매HCID 8857Ethyl Acetate용매2회

반응 조건

온도
25 °C

실험 절차

To a solution of racemic 2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid (described in Example 107) (100 g, 0.37 mol) in ethyl acetate (1.5 L) and methanol (75 mL) was added solid (1S, 2S)-(+)-pseudoephedrine (61.1 g, 0.37 mol). With efficient agitation the mixture was warmed to reflux, held at reflux for 30 min and slowly cooled to 25° C. After a minimum of 2 h the slurry was filtered and washed with ethyl acetate to yield enriched diastereomeric salt (88.6 g, 0.20 mol, 55%; diastereomeric ratio 80:20 as determined by HPLC). The enriched salt was slurried in 3% methanolic ethyl acetate (2.74 L), warmed to reflux, and held at reflux for 30 min. The slurry was cooled to 25° C. slowly, stirred for 2 h, filtered, and washed with ethyl acetate to provide additional enriched salt (70 g, 0.16 mol, 79%, diastereomeric ratio 95:5 as determined by HPLC) Treatment of the enriched salt with 5% methanolic ethyl acetate using the same procedure yielded highly enriched salt (60.0 g, 0.14 mol, 85%, diastereomeric ratio 99:1 as determined by HPLC). This salt (60 g, 0.14 mol) was added to water (1 L) and the resulting suspension acidified to pH 2-3 with concentrated hydrochloric acid (15 mL) and then extracted with diethyl ether (3×500 mL). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate and evaporated to an oil. Hexane was added and reduced in vacuo to afford enantiomerically enriched acid (36 g, 0.13 mol, 98% recovery, enantiomeric ratio 99:1 as determined by HPLC) as a white solid. Crystallisation from a mixture of hexane (360 mL) and cyclohexane (720 mL) afforded enantiomerically pure (9S,10S)-2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid as a white solid (30 g, 0.11 mol, 81%) mp 172°-173° C. [α]D =+101° (c=2, CHCl3).

후처리

  1. temperatureWith efficient agitation the mixture was warmed
  2. temperatureto reflux
  3. temperatureat reflux for 30 min
  4. filtrationAfter a minimum of 2 h the slurry was filtered
  5. washwashed with ethyl acetate
  6. customto yield
  7. temperaturewarmed
  8. temperatureto reflux
  9. temperatureat reflux for 30 min
  10. temperatureThe slurry was cooled to 25° C. slowly
  11. filtrationfiltered
  12. washwashed with ethyl acetate
  13. customto provide additional enriched salt (70 g, 0.16 mol, 79%, diastereomeric ratio 95:5 as determined by HPLC) Treatment of the enriched salt with 5% methanolic ethyl acetate using the same procedure
  14. customyielded highly enriched salt (60.0 g, 0.14 mol, 85%, diastereomeric ratio 99:1 as determined by HPLC)
  15. extractionextracted with diethyl ether (3×500 mL)
  16. washThe combined organic extracts were washed with brine
  17. dry with materialdried over anhydrous magnesium sulfate
  18. customevaporated to an oil
  19. additionHexane was added
  20. customto afford enantiomerically enriched acid (36 g, 0.13 mol, 98% recovery, enantiomeric ratio 99:1 as determined by HPLC) as a white solid
  21. customCrystallisation
  22. additionfrom a mixture of hexane (360 mL) and cyclohexane (720 mL)

출처 및 근거

ORD 기록
ord-f43f6ad8644b48d6a853b7a6d618d4b4
출처 데이터셋
uspto-grants-1993_11
특허 번호
US05266570

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