Tetrabutylammonium Fluoride → HCID 59730221, compound

HRID 130886Notes

Reaction equation

HRID 130886 reaction equation
C([Si](C)(C)[O:6][C@H:7]1[CH2:12][CH2:11][CH2:10][C@H:9]([NH:13][CH2:14][CH2:15][C:16]2[CH:31]=[CH:30][C:19]([O:20][C:21]3[CH:29]=[CH:28][C:24]([C:25]([NH2:27])=[O:26])=[CH:23][N:22]=3)=[CH:18][CH:17]=2)[CH2:8]1)(C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[OH:6][C@H:7]1[CH2:12][CH2:11][CH2:10][C@H:9]([NH:13][CH2:14][CH2:15][C:16]2[CH:31]=[CH:30][C:19]([O:20][C:21]3[CH:29]=[CH:28][C:24]([C:25]([NH2:27])=[O:26])=[CH:23][N:22]=3)=[CH:18][CH:17]=2)[CH2:8]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium Fluoride4×HCID 68748955HCID 68748955, compound

Product 1

HCID 59730221HCID 59730221, compoundYield 91.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Treat (±)-(trans)-6-(4-{2-[3-(tert-butyldimethyl-silyloxy)cyclohexylamino]ethyl}phenoxy)nicotinamide (Example 451, Part C, 63.3 mg, 0.13 mmol) in THF (1.0 mL) with 1:0 M tetrabutylammonium fluoride (TBAF) in THF (0.5 eq) for 1 hour. Add another 0.5 eq of 1.0 M TBAF and stir for 4 hours. Add 1.0 eq of 1.0 M TBAF and stir for 9 days. Add another 1.0 eq of 1.0 M TBAF and stir for 4 days. Concentrate, dissolve the mixture in CH2Cl2 (20 mL), and wash with H2O (2×20 mL), saturated aqueous NaHCO3 and brine (20 mL each). Back-extract the aqueous layers with CH2Cl2 (20 mL). Concentrate the two H2O washings and purify by flash chromatography, eluting with 15% (2.0 M NH3 in MeOH) in CH2Cl2 to afford the title compound (42.1 mg, 88%): MS ES+ 356.4 (M+H)+, HRMS calcd for C21H28N3O2 356.1974 (M+H)+, found 356.1979, time 0.41 min; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.1% TFA/water at 1.0 mL/min, 5-99% over 19 min], tR=7.11 min, 100% purity.

Workup

  1. stirringstir for 9 days
  2. stirringstir for 4 days
  3. concentrationConcentrate
  4. dissolutiondissolve the mixture in CH2Cl2 (20 mL)
  5. washwash with H2O (2×20 mL), saturated aqueous NaHCO3 and brine (20 mL each)
  6. extractionBack-extract the aqueous layers with CH2Cl2 (20 mL)
  7. concentrationConcentrate the two H2O washings
  8. custompurify by flash chromatography
  9. washeluting with 15% (2.0 M NH3 in MeOH) in CH2Cl2

Sources & evidence

ORD record
ord-502add3eaf3746948c245f5ec00711f1
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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