Acetic Acid → HCID 66932387, compound

HRID 2046734Notes

Reaction equation

HRID 2046734 reaction equation
[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:16][CH2:15][N:14]([C:17](OC(C)(C)C)=O)[CH2:13][CH2:12]1)[CH2:10][C:9]2=[O:28].CC(O)=O.C=O.[NH:36]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:38]=[CH:37]1>CO.O1CCOCC1>[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:12][CH2:13][N:14]([CH2:17][C:38]3[C:39]4[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=4)[NH:36][CH:37]=3)[CH2:15][CH2:16]1)[CH2:10][C:9]2=[O:28]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712Formaldehyde2×HCID 798IndoleHCID 52952087(E)-3-{1'-tert-butoxycarbonyl-4-oxo-spiro[chromane-2,4'-piperidine]-6-yl}-acrylic acid methyl ester2×

Product 1

HCID 66932387HCID 66932387, compoundYield 57.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (E)-3-{4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (170 mg, 0.564 mmol, Intermediate 1 free base), AcOH (0.039 ml, 0.67 mmol), and HCHO (35% in H2O, 0.055 ml, 0.67 mmol) in MeOH (8 ml) and dioxane (2 ml) was stirred at RT for 20 min and then treated with indole (94 mg, 0.80 mmol). The resulting solution was stirred at RT overnight and then further HCHO (0.02 ml) was added. After heating at 50° C. for 4 h, the solvent was evaporated and the residue was dissolved with DCM and washed with 5% aqueous NaHCO3 and brine. The organic phase was dried over Na2SO4, evaporated and the crude product was purified by column chromatography (eluent:DCM/MeOH/NH4OH 96:4:0.4) to give (E)-3-{1′-(1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester as a white solid (140 mg).

Workup

  1. stirringThe resulting solution was stirred at RT overnight
  2. temperatureAfter heating at 50° C. for 4 h
  3. customthe solvent was evaporated
  4. dissolutionthe residue was dissolved with DCM
  5. washwashed with 5% aqueous NaHCO3 and brine
  6. dry with materialThe organic phase was dried over Na2SO4
  7. customevaporated
  8. customthe crude product was purified by column chromatography (eluent:DCM/MeOH/NH4OH 96:4:0.4)

Sources & evidence

ORD record
ord-ac9365b4f6e14acca50078bea2c089a4
Source dataset
uspto-grants-2013_11
Patent number
US08592444B2

Reaction notes

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