Dichloromethane → methyl 3-(1-(4-fluorophenyl)-6-isopropyl-1H-indazol-5-yl)-2,2-dimethylpropanoate

HRID 563374Notes

Reaction equation

HRID 563374 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](CO)=[C:14]([CH:17]([CH3:19])[CH3:18])[CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:22][O:23][C:24]([O:28][Si](C)(C)C)=[C:25]([CH3:27])[CH3:26].[CH2:33](Cl)Cl>Cl[Ti](Cl)(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH2:26][C:25]([CH3:33])([CH3:27])[C:24]([O:23][CH3:22])=[O:28])=[C:14]([CH:17]([CH3:19])[CH3:18])[CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 552336Silane, ((1-methoxy-2-methyl-1-propenyl)oxy)trimethyl-HCID 67005739(1-(4-fluorophenyl)-6-isopropyl-1H-indazol-5-yl)methanol

Product 1

HCID 67005600methyl 3-(1-(4-fluorophenyl)-6-isopropyl-1H-indazol-5-yl)-2,2-dimethylpropanoateYield 47%

Reagents, catalysts & solvents 1

HCID 24193Titanium TetrachlorideCatalyst

Procedure

(1-(4-Fluorophenyl)-6-isopropyl-1H-indazol-5-yl)methanol (145 mg, 0.51 mmol) was dissolved in 5 mL of dry DCM and TiCl4 (60 mL of 1.0 M DCM solution, 60 mmol) was added portionwise and then stirred 30 min. Then the reaction was treated with 1-methoxy-2-methyl-1-(trimethylsiloxy)propene (0.2 mL, 1.0 mmol). The reaction was quenched with aqueous sodium bicarbonate and extracted 2×EtOAc, the organic layers dried over MgSO4, filtered, and concentrate. The residue was purified on SiO2 by MPLC using a 5:95 to 10:90 EtOAc/hexane gradient to give 87 mg (47% yield) of methyl 3-(1-(4-fluorophenyl)-6-isopropyl-1H-indazol-5-yl)-2,2-dimethylpropanoate. MS found: (M+H)+=369.

Workup

  1. customThe reaction was quenched with aqueous sodium bicarbonate
  2. extractionextracted 2×EtOAc
  3. dry with materialthe organic layers dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrate
  6. customThe residue was purified on SiO2 by MPLC

Sources & evidence

ORD record
ord-5ce79fefcd9c4766b019e88bb2f1589f
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

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