Hydrochloric Acid → (+/-)-8-(4-Chlorophenyl)-5-azaspiro[2.5]octan-8-ol

HRID 1016158Notes

Reaction equation

HRID 1016158 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:23])[C:13]3([CH2:15][CH2:14]3)[CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl>O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:23])[C:13]3([CH2:15][CH2:14]3)[CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 57889946Tert-butyl 8-(4-chlorophenyl)-8-hydroxy-5-azaspiro[2.5]octane-5-carboxylate

Product 1

HCID 57889353(+/-)-8-(4-Chlorophenyl)-5-azaspiro[2.5]octan-8-olYield 87%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A solution of tert-butyl 8-(4-chlorophenyl)-8-hydroxy-5-azaspiro[2.5]octane-5-carboxylate (1.81 g, 5.36 mmol) in dioxane (2 mL) was treated with 4.0 M HCl in dioxane (7 mL, 28.0 mmol), and the reaction was stirred for 30 minutes at room temperature. The mixture was concentrated in-vacuo then concentrated 2× from methylene chloride to remove residual HCl. The residue was dissolved in water and washed 2× with diethyl ether. The aqueous phase was treated with sodium bicarbonate until the mixture was basic, then washed 2× with 10 mL diethyl ether. The aqueous phase was treated with solid sodium hydroxide until the pH was >13, and the mixture was extracted 5× with ethyl acetate. The combined ethyl acetate extracts were dried over sodium sulfate and concentrated in vacuo to yield (±)-8-(4-chlorophenyl)-5-azaspiro[2.5]octan-8-ol as a colorless powder (1.1 g, 87% yield). MS (ESI+)=238.1, (M+H)+. The isomers were separated via chiral super critical fluid chromatography to yield 463 mg of isomer A and 522 mg of isomer B.

Workup

  1. concentrationThe mixture was concentrated in-vacuo
  2. concentrationthen concentrated 2× from methylene chloride
  3. customto remove residual HCl
  4. dissolutionThe residue was dissolved in water
  5. washwashed 2× with diethyl ether
  6. additionThe aqueous phase was treated with sodium bicarbonate until the mixture
  7. washwashed 2× with 10 mL diethyl ether
  8. additionThe aqueous phase was treated with solid sodium hydroxide until the pH was >13
  9. extractionthe mixture was extracted 5× with ethyl acetate
  10. dry with materialThe combined ethyl acetate extracts were dried over sodium sulfate
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-439e6323074147b593c5b7bb7d7d1a77
Source dataset
uspto-grants-2011_07
Patent number
US07985861B2

Reaction notes

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