Sodium Hydroxide → (+/-)-8-(cis 2-Phenyl-cyclohexyl)-1,4-dioxa-8-aza-spiro[4,5]decane

HRID 348537

Reaktionsgleichung

Reaktionsgleichung von HRID 348537
[C:1]1([C@H:7]2[CH2:12][CH2:11][CH2:10][CH2:9][C@H:8]2[N:13]2[CH2:18][CH2:17][C:16](=[O:19])[CH2:15][CH2:14]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1([CH:26]2CCCC[C:27]2=[O:32])C=CC=CC=1.O1C2(CCNCC2)OCC1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C1(C)C=CC=CC=1>[C:1]1([C@H:7]2[CH2:12][CH2:11][CH2:10][CH2:9][C@H:8]2[N:13]2[CH2:18][CH2:17][C:16]3([O:32][CH2:27][CH2:26][O:19]3)[CH2:15][CH2:14]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Komponenten

8

Edukt 6

HCID 14798Sodium HydroxideHCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 955922-PhenylcyclohexanoneHCID 521998p-Toluenesulfonic acid monohydrateHCID 5049666Sodium triacetoxyborohydrideHCID 69486592(+/-)-1-(cis-2-Phenyl-cyclohexyl)-piperidin-4-one

Produkt 1

HCID 69486512(+/-)-8-(cis 2-Phenyl-cyclohexyl)-1,4-dioxa-8-aza-spiro[4,5]decaneAusbeute 68 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Versuchsvorschrift

Preparation of (+/−)-cis-1-(2-Phenyl-cyclohexyl)-piperidin-4-one. To a solution of 2-phenyl-cyclohexanone (46.0 g, 264 mmol) and 1,4-dioxa-8-aza-spiro[4,5]decane (31.5 g, 220 mmol) in toluene (380 ml), p-toluenesulphonic acid monohydrate (4.18 g, 22.0 mmol) was added and the mixture was heated to reflux in an apparatus equipped with a Dean-Stark trap for 24 h. The reaction mixture was then evaporated and the resulting crude enamine dissolved in 1,2-dichloroethane (900 ml) and acetic acid (8.00 ml). To this solution, sodium triacetoxyborohydride (69.0 g, 308 mmol) was added in portion. After a total reaction time of 2.5 h, the reaction mixture was treated with 2N NaOH (250 ml) and extracted with dichloromethane. The pooled organic extracts were washed with brine, dried over magnesium sulphate, filtered and evaporated. Purification of the crude product over a silica gel plug (10:1) with n-heptane/ethyl acetate 10:1 then n-heptane/ethyl acetate 9:1 and finally ethyl acetate as eluent provided (+/−)-8-(cis-2-phenyl-cyclohexyl)-1,4-dioxa-8-aza-spiro[4,5]decane (44.8 g, 68%) as a yellow oil, MS (ISP): m/e=302.4 (M+H+).

Aufarbeitung

  1. temperaturethe mixture was heated
  2. temperatureto reflux in an apparatus
  3. customequipped with a Dean-Stark trap for 24 h
  4. customThe reaction mixture was then evaporated
  5. dissolutionthe resulting crude enamine dissolved in 1,2-dichloroethane (900 ml)
  6. extractionextracted with dichloromethane
  7. washThe pooled organic extracts were washed with brine
  8. dry with materialdried over magnesium sulphate
  9. filtrationfiltered
  10. customevaporated
  11. customPurification of the crude product over a silica gel plug (10:1) with n-heptane/ethyl acetate 10:1

Quellen und Nachweise

ORD-Eintrag
ord-733d046c4a6742d6b46547ac05cd3f13
Quelldatensatz
uspto-grants-2007_02
Patentnummer
US07176316B2

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