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

HRID 258318

反応式

HRID 258318 の反応式
[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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 6212Chloroform溶媒HCID 8857Ethyl Acetate溶媒2 回

反応条件

温度
25 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-f43f6ad8644b48d6a853b7a6d618d4b4
出典データセット
uspto-grants-1993_11
特許番号
US05266570

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