Tetrabutylammonium Fluoride → 8-(4-Fluorophenyl)-1-(3-hydroxypropyl)-N,N,2-trimethyl-1,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamide

HRID 1258472Notes

Reaction equation

HRID 1258472 reaction equation
[Si]([O:8][CH2:9][CH2:10][CH2:11][N:12]1[C:16]2[C:17]3[O:18][CH:19]([C:30]4[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=4)[CH2:20][CH2:21][C:22]=3[C:23]([C:25]([N:27]([CH3:29])[CH3:28])=[O:26])=[CH:24][C:15]=2[N:14]=[C:13]1[CH3:37])(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[F:36][C:33]1[CH:34]=[CH:35][C:30]([CH:19]2[CH2:20][CH2:21][C:22]3[C:23]([C:25]([N:27]([CH3:29])[CH3:28])=[O:26])=[CH:24][C:15]4[N:14]=[C:13]([CH3:37])[N:12]([CH2:11][CH2:10][CH2:9][OH:8])[C:16]=4[C:17]=3[O:18]2)=[CH:31][CH:32]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 672206591-(3-{[tert-Butyl(dimethyl)silyl]oxy}propyl)-8-(4-fluorophenyl)-N,N,2-trimethyl-1,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamide

Product 1

HCID 248607018-(4-Fluorophenyl)-1-(3-hydroxypropyl)-N,N,2-trimethyl-1,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamideYield 31.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To the solution of 1-(3-{[tert-butyl(dimethyl)silyl]oxy}propyl)-8-(4-fluorophenyl)-N,N,2-trimethyl-1,6,7,8-tetrahydrochromeno[7,8-d]imidazole-5-carboxamide (35 mg, 0.067 mmol, Step 9) in tetrahydrofuran was added 1M solution of tetrabutylammonium fluoride in tetrahydrofuran (0.1 mL). The mixture was stirred at room temperature for 2.5 hours. The reaction was quenched by saturated ammonium chloride aqueous solution. The mixture was extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by preparative TLC eluting with dichloromethane/methanol (20:1). The obtained product was triturated in hexane to afford the title compound as a pale yellow solid (8.6 mg, 31%)

Workup

  1. customThe reaction was quenched by saturated ammonium chloride aqueous solution
  2. extractionThe mixture was extracted with ethyl acetate
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative TLC
  7. washeluting with dichloromethane/methanol (20:1)
  8. customThe obtained product was triturated in hexane

Sources & evidence

ORD record
ord-06f9e0c11159466a90cd95edf6b38ccc
Source dataset
uspto-grants-2013_06
Patent number
US08466166B2

Reaction notes

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