dimethyl 2-((1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methyl)-2-methylmalonate → methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-(hydroxymethyl)-2-methyl-3-phenylpropanoate

HRID 563438Notes

Reaction equation

HRID 563438 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:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[C:18]([CH3:27])([C:23](OC)=[O:24])[C:19]([O:21][CH3:22])=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[C:18]([CH2:23][OH:24])([CH3:27])[C:19]([O:21][CH3:22])=[O:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

3

Reactant 1

HCID 67005816dimethyl 2-((1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methyl)-2-methylmalonate

Product 1

HCID 59252864methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-(hydroxymethyl)-2-methyl-3-phenylpropanoateYield 60.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Dissolved LiAl(OtBu)3H (509 mg, 2.0 mmol) in 2 mL THF and then added a solution of dimethyl 2-((1-(4-fluorophenyl)-1H-indazol-5-yl)(phenyl)methyl)-2-methylmalonate (215 mg, 0.48 mmol) in 2 mL of THF. After 12 h, the reaction was incomplete so more LiAl(OtBu)3H (509 mg, 2.0 mmol) was added. After 12 h, quenched with MeOH, poured into brine and extracted with EtOAc×3. The organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified on SiO2 by MPLC using a 1:3 to 1:1 EtOAc/hexane gradient. Obtained 121 mg (60% yield) of methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-2-(hydroxymethyl)-2-methyl-3-phenylpropanoate. MS found: (M+H)+=419.

Workup

  1. additionwas added
  2. waitAfter 12 h
  3. customquenched with MeOH
  4. additionpoured into brine
  5. extractionextracted with EtOAc×3
  6. dry with materialThe organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified on SiO2 by MPLC

Sources & evidence

ORD record
ord-205cffbfe78442d681845326a705eec0
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

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