Sodium Hydroxide → HCID 66932561, compound

HRID 518195Notes

Reaction equation

HRID 518195 reaction equation
[OH-].[Na+].C[O:4][C:5](=[O:29])/[CH:6]=[CH:7]/[C:8]1[CH:9]=[C:10]2[C:25](=[CH:26][CH:27]=1)[O:24][C:13]1([CH2:18][CH2:17][N:16]([C:19](=[O:23])[NH:20][CH2:21][CH3:22])[CH2:15][CH2:14]1)[CH2:12][C:11]2=[O:28]>O1CCOCC1.O>[CH2:21]([NH:20][C:19]([N:16]1[CH2:17][CH2:18][C:13]2([CH2:12][C:11](=[O:28])[C:10]3[C:25](=[CH:26][CH:27]=[C:8](/[CH:7]=[CH:6]/[C:5]([OH:29])=[O:4])[CH:9]=3)[O:24]2)[CH2:14][CH2:15]1)=[O:23])[CH3:22]

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 66932624HCID 66932624, compound

Product 1

HCID 66932561HCID 66932561, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

4 M NaOH (0.148 ml, 0.591 mmol) was added to a solution of (E)-3-{1′-ethylcarbamoyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (220 mg, 0.591 mmol) in dioxane (3 ml) and water (3 ml) and the mixture was stirred at RT for 1 h. Further 4 M NaOH (0.073 ml) was added and the mixture was stirred for additional 2 h. Dioxane was removed under vacuum and the residue was acidified with 2 M HCl. The resulting precipitate was filtered to give (E)-3-{1′-ethylcarbamoyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid. The crude compound (163 mg) was dissolved in a mixture of DCM (3 ml) and TEA (0.126 ml, 0.91 mmol). EDC (174 mg, 0.91 mmol) and HOBT (61 mg, 0.45 mmol) were added at 0° C. and the resulting solution was stirred at RT for 1 h. NH2OTHP (66 mg, 0.56 mmol) was added and the mixture was stirred at RT for 4 h and then washed with 5% aqueous solution of NaHCO3. The organic phase was washed with water, dried over Na2SO4 and evaporated. The crude residue was purified by column chromatography (eluent: DCM/MeOH/NH4OH 97:3:0.3) and the resulting (E)-3-{1′-ethylcarbamoyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide was dissolved in DCM and treated with 4 M HCl in dioxane for 2 h. The precipitate was filtered and washed with DCM to give the title compound as a pale yellow powder (118 mg).

Workup

  1. stirringthe mixture was stirred for additional 2 h
  2. customDioxane was removed under vacuum
  3. filtrationThe resulting precipitate was filtered

Sources & evidence

ORD record
ord-b79caef4db294c179a26edd22e0864ec
Source dataset
uspto-grants-2015_08
Patent number
US09115148B2

Reaction notes

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