Hydrochloric Acid → 2-(4-((R)-2,2,2-trifluoro-1-methoxyethyl)phenyl)-2-azaspiro[4.5]decane-1,8-dione

HRID 1023645Notes

Reaction equation

HRID 1023645 reaction equation
[F:1][C:2]([F:28])([F:27])[C@@H:3]([C:6]1[CH:11]=[CH:10][C:9]([N:12]2[CH2:25][CH2:24][C:14]3([CH2:23][CH2:22][C:17]4(OCC[O:18]4)[CH2:16][CH2:15]3)[C:13]2=[O:26])=[CH:8][CH:7]=1)[O:4][CH3:5].Cl.C([O-])([O-])=O.[Na+].[Na+]>O1CCCC1>[F:28][C:2]([F:1])([F:27])[C@@H:3]([C:6]1[CH:7]=[CH:8][C:9]([N:12]2[CH2:25][CH2:24][C:14]3([CH2:23][CH2:22][C:17](=[O:18])[CH2:16][CH2:15]3)[C:13]2=[O:26])=[CH:10][CH:11]=1)[O:4][CH3:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 6822762810-[4-((R)-2,2,2-Trifluoro-1-methoxy-ethyl)-phenyl]-1,4-dioxa-10-aza-dispiro[4.2.4.2]tetradecan-9-one

Product 1

HCID 682275902-(4-((R)-2,2,2-trifluoro-1-methoxyethyl)phenyl)-2-azaspiro[4.5]decane-1,8-dioneYield 99.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

10-[4-((R)-2,2,2-Trifluoro-1-methoxy-ethyl)-phenyl]-1,4-dioxa-10-aza-dispiro[4.2.4.2]tetradecan-9-one (1.41 g) was dissolved in tetrahydrofuran (35.0 mL). Then hydrochloric acid (2M, 21.2 mL) was added dropwise over a period of 15 minutes to the reaction mixture. The mixture was stirred for 4.5 hours at RT and was then poured into ice/water and basified with saturated Na2CO3 solution. The aqueous phase was then extracted two times with ethyl acetate and the organic layers were washed brine, dried over Na2SO4, filtered and the solvent was evaporated. The crude material was purified by flash chromatography (gradient of ethyl acetate in heptane) to provide the title compound as a colorless solid (1.25 g). MS (ESI): 356.1 (MH+).

Workup

  1. extractionThe aqueous phase was then extracted two times with ethyl acetate
  2. washthe organic layers were washed brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent was evaporated
  6. customThe crude material was purified by flash chromatography (gradient of ethyl acetate in heptane)

Sources & evidence

ORD record
ord-c4c9fd4f913342fd8934a14842955c8d
Source dataset
uspto-grants-2014_05
Patent number
US08722721B2

Reaction notes

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