Triacetoxyperiodinane → 1,1,1-Trifluoro-4-(1-(4-fluorophenyl)-1h-indazol-5-yl)-3,3-dimethyl-4-phenylbutan-2-one

HRID 218183Notes

Reaction equation

HRID 218183 reaction equation
[F:1][C:2]([F:32])([F:31])[CH:3]([OH:30])[C:4]([CH3:29])([CH3:28])[CH:5]([C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[N:17]([C:21]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=1)[N:16]=[CH:15]2)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[F:32][C:2]([F:1])([F:31])[C:3](=[O:30])[C:4]([CH3:29])([CH3:28])[CH:5]([C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[N:17]([C:21]1[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=1)[N:16]=[CH:15]2)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

4

Reactant 2

HCID 159087TriacetoxyperiodinaneHCID 687027771,1,1-trifluoro-4-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3,3-dimethyl-4-phenylbutan-2-ol

Product 1

HCID 592510641,1,1-Trifluoro-4-(1-(4-fluorophenyl)-1h-indazol-5-yl)-3,3-dimethyl-4-phenylbutan-2-oneYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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. filtrationwas filtered through a plug of SiO2
  2. concentrationconcentrated
  3. customto give the crude product
  4. customThe crude material was purified via chromatography on silica gel eluting with 10% ethyl acetate in hexane

Sources & evidence

ORD record
ord-5fa64046a2084d80b7eb9d80be187d01
Source dataset
uspto-grants-2012_06
Patent number
US08198311B2

Reaction notes

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