Tetrabutylammonium Fluoride → HCID 178447113, compound

HRID 1046587Notes

Reaction equation

HRID 1046587 reaction equation
C([Si]([C:8]1[C:13]([F:14])=[C:12]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[CH:21][CH:22]=3)[NH:17][N:16]=2)[N:11]=[C:10]([N:24]2[CH2:29][CH2:28][NH:27][C@H:26]([C@:30]([CH3:39])([O:34][Si](C)(C)C)[CH:31]([CH3:33])[CH3:32])[CH2:25]2)[C:9]=1[F:40])(C)C)(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CCOC(C)=O>[F:40][C:9]1[C:10]([N:24]2[CH2:29][CH2:28][NH:27][C@H:26]([C@:30]([OH:34])([CH:31]([CH3:32])[CH3:33])[CH3:39])[CH2:25]2)=[N:11][C:12]([C:15]2[C:23]3[C:18](=[N:19][CH:20]=[CH:21][CH:22]=3)[NH:17][N:16]=2)=[C:13]([F:14])[CH:8]=1

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 178447657HCID 178447657, compound

Product 1

HCID 178447113HCID 178447113, compoundYield 84.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

tert-butyl-[2-[(3S)-3-[(1R)-1,2-dimethyl-1-trimethylsilyloxy-propyl]piperazin-1-yl]-3,5-difluoro-6-(1H-pyrazolo[3,4-b]pyridin-3-yl)-4-pyridyl]-dimethyl-silane (60 g, 101.9 mmol) was dissolved in THF (216.0 mL) at room temperature. TBAF in THF (214.0 mL of 1 M, 214.0 mmol) was added dropwise via cannula to the brown solution over 45 minutes. The reaction was stirred overnight, after which time the deprotection was complete by Lc/Ms. The mixture was diluted with EtOAc (600 ml) and washed with saturated aqueous NaHCO3 (100 ml then 2×200 ml). The organic phase was further washed with a 2:3 mixture of saturated brine:water (100 ml) until no remaining Bu4N+ salts were observed Lc/Ms analysis. The organic phase was dried over MgSO4, filtered and concentrated in vacuo to give a brown solid. The solid was triturated with diethyl ether, filtered and dried to give a orange brown solid (34.5 g, 84%). The solid was recrystallised from isopropanol. This afforded the title compound as a beige solid (23 g); 1H NMR (d6-DMSO) 0.84 (3H, d), 0.90 (3H, d), 1.06 (3H, s), 1.83 (2H, m), 2.74 (2H, d), 2.85 (2H, d), 3.09 (1H, d), 3.78 (1H, d), 4.04 (1H, d), 4.13 (1H, s), 7.30 (1H, dd), 7.92 (1H, dd), 8.60 (1H, dd), 8.77 (1H, dd), 13.99 (1H, brs); 19F NMR (decoupled) −128.5, −124.1; MS ES(+) 403.0 (M+1).

Workup

  1. washwashed with saturated aqueous NaHCO3 (100 ml
  2. washThe organic phase was further washed with a 2:3 mixture of saturated brine
  3. dry with materialThe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a brown solid
  7. customThe solid was triturated with diethyl ether
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-d4a5f586bddf466d9c1a5c4bcc08eb92
Source dataset
uspto-grants-2013_10
Patent number
US08569337B2

Reaction notes

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