Hydrochloric Acid → 2-[4-(2,2,2-Trifluoro-1-hydroxy-ethyl)-phenyl]-2-aza-spiro[4.5]decane-1,8-dione

HRID 2092675Notes

Reaction equation

HRID 2092675 reaction equation
[F:1][C:2]([F:27])([F:26])[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:24][CH2:23][C:13]3([CH2:22][CH2:21][C:16]4(OCC[O:17]4)[CH2:15][CH2:14]3)[C:12]2=[O:25])=[CH:7][CH:6]=1)[OH:4].Cl>O1CCCC1>[F:27][C:2]([F:1])([F:26])[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH2:24][CH2:23][C:13]3([CH2:14][CH2:15][C:16](=[O:17])[CH2:21][CH2:22]3)[C:12]2=[O:25])=[CH:7][CH:6]=1)[OH:4]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 6658017410-[4-(2,2,2-Trifluoro-1-hydroxy-ethyl)-phenyl]-1,4-dioxa-10-aza-dispiro[4.2.4.2]tetradecan-9-one

Product 1

HCID 665802062-[4-(2,2,2-Trifluoro-1-hydroxy-ethyl)-phenyl]-2-aza-spiro[4.5]decane-1,8-dioneYield 74.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

10-[4-(2,2,2-Trifluoro-1-hydroxy-ethyl)-phenyl]-1,4-dioxa-10-aza-dispiro[4.2.4.2]tetradecan-9-one (402 mg, obtained in example 133, step 4) was dissolved in tetrahydrofuran (10 mL). Then, hydrochloric acid (2M, 5.22 mL) was added dropwise over a period of 10 minutes to the reaction mixture. The mixture was stirred for 3 hours at RT. The reaction mixture was poured into ice/water and was extracted two times with ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, filtered and the solvent was evaporated. The residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate) to give the title compound as a colorless foam (265 mg, 73%). MS (m/e): 342.1 [MH+].

Workup

  1. extractionwas extracted two times with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent was evaporated
  6. customThe residue was purified by flash chromatography (silica gel, gradient of heptane in ethyl acetate)

Sources & evidence

ORD record
ord-729874c4adc5420d80f00c121fd6de79
Source dataset
uspto-grants-2013_05
Patent number
US08440710B2

Reaction notes

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