(Trifluoromethyl)trimethylsilane → 1,1,1-trifluoro-4-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3,3-dimethyl-4-phenylbutan-2-ol

HRID 218182Notes

Reaction equation

HRID 218182 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C:18]([CH3:22])([CH3:21])[CH:19]=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.C[Si](C)(C)[C:31]([F:34])([F:33])[F:32].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[F:32][C:31]([F:34])([F:33])[CH:19]([OH:20])[C:18]([CH3:22])([CH3:21])[CH:17]([C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=1)[N:9]=[CH:10]2)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 592510413-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanal

Product 1

HCID 687027771,1,1-trifluoro-4-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3,3-dimethyl-4-phenylbutan-2-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2,2-dimethyl-3-phenylpropanal (from Ex 109(b), (140 mg, 0.376 mmol) in THF (3 ml) at 0° C. was added trimethyl(trifluoromethyl)silane (267 mg, 1.88 mmol) and tetrabutyl-ammonium fluoride in THF (0.376 ml, 0.376 mmol, 1M THF solution). The reaction mixture was stirred at 0° C. for 30 minutes, and then at room temperature overnight. After quenching with 4N HCl, the reaction was stirred for 30 minutes and was extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4 and concentrated to give the crude 1,1,1-trifluoro-4-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3,3-dimethyl-4-phenylbutan-2-ol. The crude alcohol in DCM (1 ml) was treated with commercially available Dess-Martin periodinane (187 mg, 0.440 mmol). The reaction was complete in 45 minutes and was filtered through a plug of SiO2 using DCM and concentrated to give the crude product. The crude material was purified via chromatography on silica gel eluting with 10% ethyl acetate in hexane to afford the compound of Example 6 as a colorless viscous oil (90 mg, 70% yield). 1H NMR (400 MHz, MeOD) δ ppm 8.21 (1 H, s) 7.85 (1 H, s) 7.70 (2 H, dd, J=9.16, 4.58 Hz) 7.63 (1 H, d, J=8.65 Hz) 7.43 (1 H, dd, J=8.90, 1.78 Hz) 7.37 (2 H, d, J=7.12 Hz) 7.27-7.33 (4 H, m) 7.22 (1 H, t, J=7.12 Hz) 4.80 (1 H, s) 1.43 (6 H, d, J=5.09 Hz). LC/MS (m/z) 441.24 [(M+H)+]; HPLC Rt: 4.066 min.

Workup

  1. customat room temperature
  2. customovernight
  3. customAfter quenching with 4N HCl
  4. stirringthe reaction was stirred for 30 minutes
  5. extractionwas extracted with ethyl acetate
  6. washThe organic phase was washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-be042ce906204a7b8ade7fccc8954266
Source dataset
uspto-grants-2012_06
Patent number
US08198311B2

Reaction notes

Loading…