Acetic Acid → HCID 66932316, compound

HRID 2046736Notes

Reaction equation

HRID 2046736 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.[F:36][C:37]1[CH:45]=[C:44]2[C:40]([CH:41]=[CH:42][NH:43]2)=[CH:39][CH:38]=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:41]3[C:40]4[C:44](=[CH:45][C:37]([F:36])=[CH:38][CH:39]=4)[NH:43][CH:42]=3)[CH2:15][CH2:16]1)[CH2:10][C:9]2=[O:28]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 3512786-FluoroindoleHCID 52952087(E)-3-{1'-tert-butoxycarbonyl-4-oxo-spiro[chromane-2,4'-piperidine]-6-yl}-acrylic acid methyl ester2×

Product 1

HCID 66932316HCID 66932316, compoundYield 55.3%

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 (0.051 ml, 0.90 mmol), and HCHO (35% in H2O, 0.07 ml, 0.847 mmol) in MeOH (12 ml) and dioxane (3 ml) was stirred at RT for 20 min and then treated with 6-fluoro-1H-indole (100 mg, 0.734 mmol). The resulting solution was stirred at 50° C. for 1 h. The solvent was then evaporated, the residue dissolved with DCM and washed with 5% aqueous NaHCO3 and brine. The organic phase was dried over Na2SO4 and evaporated under vacuum. The crude mixture was purified by column chromatography (eluent:DCM/MeOH/NH4OH 97:3:0.3) to give (E)-3-{1′-(6-fluoro-1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester as a brown solid (140 mg).

Workup

  1. stirringThe resulting solution was stirred at 50° C. for 1 h
  2. customThe solvent was then evaporated
  3. dissolutionthe residue dissolved with DCM
  4. washwashed with 5% aqueous NaHCO3 and brine
  5. dry with materialThe organic phase was dried over Na2SO4
  6. customevaporated under vacuum
  7. customThe crude mixture was purified by column chromatography (eluent:DCM/MeOH/NH4OH 97:3:0.3)

Sources & evidence

ORD record
ord-ea51abb5ec7347e0b5d4f92c0f1f4aaa
Source dataset
uspto-grants-2013_11
Patent number
US08592444B2

Reaction notes

Loading…