(Z)-(1-(benzyloxy)prop-1-enyloxy)trimethylsilane → 4-(3-(benzyloxy)-1-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-oxopropyl)benzoic acid

HRID 563433Notes

Reaction equation

HRID 563433 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](O)[C:18]4[CH:26]=[CH:25][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=4)=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH2:28]([O:35]/[C:36](/[O:39][Si](C)(C)C)=[CH:37]/[CH3:38])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[CH2:28]([O:35][C:36](=[O:39])[CH:37]([CH3:38])[CH:17]([C:18]1[CH:26]=[CH:25][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=1)[C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[N:9]=[CH:10]2)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

5

Reactant 2

HCID 59252750(Z)-(1-(benzyloxy)prop-1-enyloxy)trimethylsilaneHCID 670059404-((1-(4-fluorophenyl)-1H-indazol-5-yl)(hydroxy)methyl)benzoic acid

Product 1

HCID 592528604-(3-(benzyloxy)-1-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-oxopropyl)benzoic acidYield 55.1%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-((1-(4-fluorophenyl)-1H-indazol-5-yl)(hydroxy)methyl)benzoic acid (180 mg, 0.5 mmol) and (Z)-(1-(benzyloxy)prop-1-enyloxy)trimethylsilane (10.0 mmol, prepared using General Silyl Ketene Acetal Method A) in 10 mL of dry DCM was added TiCl4 (1.0 mL of 1.0 M DCM solution, 1.0 mmol) and then stirred 3 h. The reaction was quenched with MeOH, poured into aqueous sodium bicarbonate and extracted 2×EtOAc. The organic layers were dried over MgSO4, filtered, and concentrated. MPLC purification on SiO2 using a 0-100% EtOAc/hexane gradient gave 140 mg (55% yield) of 4-(3-(benzyloxy)-1-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-methyl-3-oxopropyl)benzoic acid. MS found: (M+H)+=509.

Workup

  1. customThe reaction was quenched with MeOH
  2. additionpoured into aqueous sodium bicarbonate
  3. extractionextracted 2×EtOAc
  4. dry with materialThe organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customMPLC purification on SiO2 using a 0-100% EtOAc/hexane gradient

Sources & evidence

ORD record
ord-7761a26b696a41dca2c9053765485b3e
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

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