Tetrabutylammonium Fluoride → N-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-(1-hydroxycyclopropyl)phenyl)propanamide

HRID 1842905Notes

Reaction equation

HRID 1842905 reaction equation
[Si]([O:8][C:9]1([C:12]2[CH:17]=[CH:16][C:15]([CH:18]([CH3:39])[C:19]([NH:21][CH2:22][C:23]3[N:27]([C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=4)[N:26]=[C:25]([C:35]([F:38])([F:37])[F:36])[CH:24]=3)=[O:20])=[CH:14][C:13]=2[F:40])[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:34][C:30]1[CH:29]=[C:28]([N:27]2[C:23]([CH2:22][NH:21][C:19](=[O:20])[CH:18]([C:15]3[CH:16]=[CH:17][C:12]([C:9]4([OH:8])[CH2:10][CH2:11]4)=[C:13]([F:40])[CH:14]=3)[CH3:39])=[CH:24][C:25]([C:35]([F:38])([F:36])[F:37])=[N:26]2)[CH:33]=[CH:32][CH:31]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 708159202-(4-(1-(tert-butyldimethylsilyloxy)-cyclopropyl)-3-fluorophenyl)-N-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)propanamide

Product 1

HCID 70816389N-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-(1-hydroxycyclopropyl)phenyl)propanamideYield 49.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 2-(4-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)-N-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-propanamide (103 mg, 0.173 mmol, 1 eq) in THF (5 mL) was added TBAF (90 mg, 0.346 mmol, 2 eq) at room temperature and the mixture was stirred for 2 h after which THF was evaporated and the residue was dissolved in ethyl acetate (15 mL), washed with water (10 mL×2), brine (10 mL) and the solvent evaporated. The residue was purified by CC using methanol/CHCl3 (1:9) as eluent to give N-((1-(3-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)methyl)-2-(3-fluoro-4-(1-hydroxycyclopropyl)phenyl)propanamide (41 mg, 49%) as off white solid (TLC system: methanol/CHCl3 (1:9) Rf: 0.5).

Workup

  1. customwas evaporated
  2. dissolutionthe residue was dissolved in ethyl acetate (15 mL)
  3. washwashed with water (10 mL×2), brine (10 mL)
  4. customthe solvent evaporated
  5. customThe residue was purified by CC

Sources & evidence

ORD record
ord-d2f300212ec24e19a8895dede55a2924
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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