Dichloromethane → methyl 3-(1H-indazol-5-yl)-2-methyl-3-phenylpropanoate

HRID 563424Notes

Reaction equation

HRID 563424 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)O)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[CH3:18][O:19][C:20]([O:23][Si](C)(C)C)=[CH:21][CH3:22].C(Cl)Cl>CC#N.Cl[Ti](Cl)(Cl)Cl>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([CH:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:21]([CH3:22])[C:20]([O:19][CH3:18])=[O:23])=[CH:7][CH:8]=2)[CH:3]=[N:2]1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 534224851-Methoxyprop-1-enoxy(trimethyl)silane2×HCID 59252753(1H-Indazol-5-yl)(phenyl)methanol

Product 1

HCID 59252770methyl 3-(1H-indazol-5-yl)-2-methyl-3-phenylpropanoate

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

To a solution of (1H-indazol-5-yl)(phenyl)methanol (180 mg, 0.71 mmol) and (1-methoxyprop-1-enyloxy)trimethylsilane (0.32 mL, 1.78 mmol) in 10 mL of dry MeCN was added TiCl4 (2.5 mL of 1.0 M DCM solution, 2.5 mmol) and then stirred 1 h. The reaction was incomplete so added 10 mL of DCM and additional (1-methoxyprop-1-enyloxy)trimethylsilane (0.3 mL, 1.7 mmol) After 1 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. HPLC purification resulted in the resolution of the two diastereomers of methyl 3-(1H-indazol-5-yl)-2-methyl-3-phenylpropanoate which were taken independently to the next step. MS found: (M+H)+=295.

Workup

  1. customAfter 1 h
  2. customthe reaction was quenched with MeOH
  3. additionpoured into aqueous sodium bicarbonate
  4. extractionextracted 2×EtOAc
  5. dry with materialThe organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customHPLC purification

Sources & evidence

ORD record
ord-ca8b6e25b9534f9899b05176e8e71afc
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

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