1,4-Dioxa-8-azaspiro(4.5)decane → HCID 71093395, compound

HRID 1472752Notes

Reaction equation

HRID 1472752 reaction equation
C1(C(O)(C2C=CC=CC=2)C(OCC2CCN(CCCCCC=O)CC2)=O)CCCCC1.[CH:32]1([C:38]([OH:65])([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[C:39]([O:41][CH2:42][CH:43]2[CH2:48][CH2:47][N:46]([CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH:54]3OCCO3)[CH2:45][CH2:44]2)=[O:40])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1.O1[C:70]2([CH2:75][CH2:74][NH:73][CH2:72][CH2:71]2)[O:69]CC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[CH:32]1([C:38]([OH:65])([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)[C:39]([O:41][CH2:42][CH:43]2[CH2:44][CH2:45][N:46]([CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][N:73]3[CH2:74][CH2:75][C:70](=[O:69])[CH2:71][CH2:72]3)[CH2:47][CH2:48]2)=[O:40])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]1

Participants

6

Reactant 4

HCID 674351,4-Dioxa-8-azaspiro(4.5)decaneHCID 5049666Sodium triacetoxyborohydrideHCID 71245516HCID 71245516, compoundHCID 86676458HCID 86676458, compound

Product 1

HCID 71093395HCID 71093395, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (1-(6-oxohexyl)piperidin-4-yl)methyl 2-cyclohexyl-2-hydroxy-2-phenylacetate (prepared as Preparation intermediate 15 but using (1-(5-(1,3-dioxolan-2-yl)pentyl)piperidin-4-yl)methyl 2-cyclohexyl-2-hydroxy-2-phenylacetate (0.20 g, 0.47 mmol) and 1,4-dioxa-8-azaspiro[4.5]decane (0.133 g, 0.93 mmol) in THF (5 mL), sodium triacetoxyborohydride (0.294 g, 1.39 mmol) was added. The reaction mixture was stirred at RT for 18 hours. The reaction mixture was partitioned between DCM and saturated aqueous sodium hydrogen carbonate. The organic phase was removed, and the aqueous phase was extracted with further DCM. The combined organics were dried (magnesium sulfate), filtered, and concentrated under reduced pressure. The crude product was dissolved in THF (2 mL) and 2M aqueous HCl and heated at 60° C. for 18 hours. The reaction mixture was allowed to cool to RT and then quenched with saturated aqueous sodium hydrogen carbonate. The mixture was extracted twice with ethyl acetate. The organic phases were dried (magnesium sulfate), filtered and concentrated under reduced pressure. The product was isolated (0.193 g, 80%).

Workup

  1. additionwas added
  2. customThe reaction mixture was partitioned between DCM and saturated aqueous sodium hydrogen carbonate
  3. customThe organic phase was removed
  4. extractionthe aqueous phase was extracted with further DCM
  5. dry with materialThe combined organics were dried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe crude product was dissolved in THF (2 mL)
  9. temperature2M aqueous HCl and heated at 60° C. for 18 hours
  10. temperatureto cool to RT
  11. customquenched with saturated aqueous sodium hydrogen carbonate
  12. extractionThe mixture was extracted twice with ethyl acetate
  13. dry with materialThe organic phases were dried (magnesium sulfate)
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe product was isolated (0.193 g, 80%)

Sources & evidence

ORD record
ord-3dd984b4605e415fafe1ae3b6c2b8d2a
Source dataset
uspto-grants-2015_04
Patent number
US09012644B2

Reaction notes

Loading…