Hydrochloric Acid → HCID 69337544, compound

HRID 1179074Notes

Reaction equation

HRID 1179074 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH2:13].[CH3:14][N:15]([CH3:29])[C:16]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[ClH:44]>C(O)C.C(O)(=O)C.ClCCCl.O1CCCC1>[ClH:44].[ClH:44].[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH:13][CH:19]1[CH2:18][CH2:17][C:16]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)([N:15]([CH3:29])[CH3:14])[CH2:21][CH2:20]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 1646825-FluorotryptamineHCID 5049666Sodium triacetoxyborohydrideHCID 114244924-(Dimethylamino)-4-phenylcyclohexan-1-one

Product 1

HCID 69337544HCID 69337544, compound

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of tetrahydrofuran (12 ml) and 1,2-dichloroethane (4 ml) there were added, under argon, first 2-(5-fluoro-1H-indol-3-yl)ethylamine (282 mg) and 4-dimethylamino-4-phenylcyclohexanone (343 mg), and acetic acid (0.09 ml) was added thereto. After 15 minutes, NaBH(OAc)3 (474 mg) was added, and stirring was carried out for 40 hours at RT. The reaction mixture was concentrated, and the residue was taken up in 1M hydrochloric acid (20 ml) and extracted with ether (2×30 ml). A white precipitate (191 mg) separated out here and was separated off. The aqueous solution was then rendered alkaline with 1M NaOH (28 ml) and extracted with ether (2×30 ml) and ethyl acetate (2×30 ml). The combined organic extracts were dried over sodium sulfate and concentrated. The residue (468 mg) consisted of two products, just like the solid separated off previously. They were together (459 mg) purified by column chromatography with methanol/ammonia (500:1). The nonpolar diastereomer was obtained as a white solid (218 mg; m.p. 191-192° C.), was dissolved in ethanol (15 ml), with heating, and 3.3N ethanolic hydrochloric acid (0.47 ml, 1.56 mmol.) was added thereto. Because no solid had yet precipitated after 90 minutes, 2-butanone (5 ml) was added. Crystallisation of the hydrochloride then began after a short time (184 mg; m.p. 230-237° C.).

Workup

  1. additionwere added, under argon
  2. waitwas carried out for 40 hours at RT
  3. concentrationThe reaction mixture was concentrated
  4. extractionextracted with ether (2×30 ml)
  5. customA white precipitate (191 mg) separated out here and
  6. customwas separated off
  7. extractionextracted with ether (2×30 ml) and ethyl acetate (2×30 ml)
  8. dry with materialThe combined organic extracts were dried over sodium sulfate
  9. concentrationconcentrated
  10. customseparated off previously
  11. custompurified by column chromatography with methanol/ammonia (500:1)
  12. customThe nonpolar diastereomer was obtained as a white solid (218 mg; m.p. 191-192° C.)
  13. temperaturewith heating
  14. customBecause no solid had yet precipitated after 90 minutes
  15. addition2-butanone (5 ml) was added
  16. customCrystallisation of the hydrochloride

Sources & evidence

ORD record
ord-9cc4a8279c5545ae8120ca5d62c5a39c
Source dataset
uspto-grants-2007_10
Patent number
US07276518B2

Reaction notes

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