Tetrabutylammonium Fluoride → 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-6-(4-hydroxypiperidine-1-carbonyl)-2-morpholino-4H-chromen-4-one

HRID 1187236Notes

Reaction equation

HRID 1187236 reaction equation
[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:36][CH:37]1[CH2:42][CH2:41][N:40]([C:43]([C:45]2[CH:46]=[C:47]3[C:52](=[C:53]([CH:55]([N:57]([C:59]4[CH:64]=[C:63]([F:65])[CH:62]=[C:61]([F:66])[CH:60]=4)[CH3:58])[CH3:56])[CH:54]=2)[O:51][C:50]([N:67]2[CH2:72][CH2:71][O:70][CH2:69][CH2:68]2)=[CH:49][C:48]3=[O:73])=[O:44])[CH2:39][CH2:38]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1>C1COCC1>[F:66][C:61]1[CH:60]=[C:59]([N:57]([CH3:58])[CH:55]([C:53]2[CH:54]=[C:45]([C:43]([N:40]3[CH2:39][CH2:38][CH:37]([OH:36])[CH2:42][CH2:41]3)=[O:44])[CH:46]=[C:47]3[C:52]=2[O:51][C:50]([N:67]2[CH2:72][CH2:71][O:70][CH2:69][CH2:68]2)=[CH:49][C:48]3=[O:73])[CH3:56])[CH:64]=[C:63]([F:65])[CH:62]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 671037136-(4-(tert-butyldiphenylsilyloxy)piperidine-1-carbonyl)-8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-2-morpholino-4H-chromen-4-one

Product 1

HCID 582349708-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-6-(4-hydroxypiperidine-1-carbonyl)-2-morpholino-4H-chromen-4-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Tetrabutylammonium fluoride (1N in THF) (7.83 mL, 7.83 mmol) was added dropwise to a stirred solution of 6-(4-(tert-butyldiphenylsilyloxy)piperidine-1-carbonyl)-8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-2-morpholino-4H-chromen-4-one (3 g, 3.92 mmol, enantiomer 2 in Example 7.0a, [α]D20°: −102° dissolved in THF (20 mL) at RT under nitrogen and stirred for 2 hrs. The mixture was evaporated to dryness, diluted with DCM, washed with water. The organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (80 g) eluting with 3 to 7% MeOH in DCM. The solvent was evaporated to dryness to give a foam which was triturated in ether (2-5 mL). The resulting white solid was collected by filtration and dried to give 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-6-(4-hydroxypiperidine-1-carbonyl)-2-morpholino-4H-chromen-4-one enantiomer 2 (1.7 g, 82%) as a white solid. Mass Spectrum: M+H° 528. [α]D20°: +7° in MeCN.

Workup

  1. customThe mixture was evaporated to dryness
  2. additiondiluted with DCM
  3. washwashed with water
  4. washThe organic phase was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash chromatography on silica gel (80 g)
  9. washeluting with 3 to 7% MeOH in DCM
  10. customThe solvent was evaporated to dryness
  11. customto give a foam which
  12. customwas triturated in ether (2-5 mL)
  13. filtrationThe resulting white solid was collected by filtration
  14. customdried

Sources & evidence

ORD record
ord-82c83f878ba84c89894aee719bcdfb90
Source dataset
uspto-grants-2014_03
Patent number
US08673906B2

Reaction notes

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