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

HRID 862722Notes

Reaction equation

HRID 862722 reaction equation
[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

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent3×

Conditions

Temperature
25 °C

Procedure

To a solution of racemic 2-chloro-9,10-dihydro-9,10-methano-9-anthracenecarboxylic acid (100 g; 0.37M) in ethyl acetate (1.5 L) and methanol (75 mL) was added solid (1S,2S)-(+)-pseudoephedrine (61.1 g; 0.37M). With efficient agitation the mixture was warmed to reflux, held for 30 minutes 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; 0.20M; 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, held 30 minutes,cooled to 25 C. slowly, held 2 h and then filtered and washed with ethyl acetate to provide further enriched salt (70 g; 0.16M; 79%; diastereomeric ratio 95:5, as determined by HPLC). Treatment of the further enriched salt with 5% methanolic ethyl acetate using the same procedure yielded highly enriched salt (60.0 g; 0.14M; 85%; diastereomeric ratio 99:1, as determined by HPLC). This salt (60 g; 0.14M) was added to water (1 L) and the consequent 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 (MgSO4) and evaporated to an oil. Hexane was added and evaporated to afford enantiomerically enriched acid (36 g; 0.13M; 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-anthracene-carboxylic acid as a white solid (30 g, 0.11 mol, 81%) mp 172°-173° C. αD =+101° (c=2.0, CHCl3).

Workup

  1. temperatureWith efficient agitation the mixture was warmed
  2. temperatureto reflux
  3. filtrationAfter a minimum of 2 h the slurry was filtered
  4. washwashed with ethyl acetate
  5. customto yield
  6. temperaturewarmed
  7. temperatureto reflux
  8. waitheld 30 minutes
  9. temperaturecooled to 25 C
  10. waitslowly, held 2 h
  11. filtrationfiltered
  12. washwashed with ethyl acetate
  13. customto provide further enriched salt (70 g; 0.16M; 79%; diastereomeric ratio 95:5, as determined by HPLC)
  14. extractionextracted with diethyl ether (3×500 mL)
  15. washThe combined organic extracts were washed with brine
  16. dry with materialdried (MgSO4)
  17. customevaporated to an oil
  18. additionHexane was added
  19. customevaporated
  20. customto afford enantiomerically enriched acid (36 g; 0.13M; 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)

Sources & evidence

ORD record
ord-74786af88ce14738a1b65f4b2cbe3b9f
Source dataset
uspto-grants-1998_02
Patent number
US05719166

Reaction notes

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