Hydrochloric Acid → 4-(4',5'-difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-1H-indazole

HRID 551494Notes

Reaction equation

HRID 551494 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]3[CH:25]=[CH:24][CH:23]=[C:22]4[C:18]=3[CH:19]=[N:20][N:21]4C3CCCCO3)=[CH:11][CH:10]=2)=[C:4]([O:32][CH3:33])[CH:3]=1.Cl.CCOC(C)=O.O>CO>[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([C:9]2[CH:10]=[CH:11][C:12]([O:15][CH2:16][C:17]3[CH:25]=[CH:24][CH:23]=[C:22]4[C:18]=3[CH:19]=[N:20][NH:21]4)=[CH:13][CH:14]=2)=[C:4]([O:32][CH3:33])[CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962Water2×HCID 8857Ethyl AcetateHCID 671519344-(4',5'-difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-1-(tetrahydro-pyran-2-yl)-1H-indazole

Product 1

HCID 529396104-(4',5'-difluoro-2'-methoxy-biphenyl-4-yloxymethyl)-1H-indazoleYield 73.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

4-(4′,5′-Difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-1-(tetrahydro-pyran-2-yl)-1H-indazole (0.4 g, 0.888 mmol) and 1N HCl (1.8 mL, 1.8 mmol) in 10 mL MeOH were heated to reflux for 5 hrs. The reaction was cooled and distributed between EtOAc and H2O. The water layer was made basic to pH 12 and the organic layer was separated and concentrated in vacuo. The crude product was purified by flash chromatography with a gradient from 20-100% ethyl acetate in hexanes to yield 4-(4′,5′-difluoro-2′-methoxy-biphenyl-4-yloxymethyl)-1H-indazole as a white solid (240 mg, 73.7%). LC-MS (ES) calculated for C21H16F2N2O2, 366.37; found m/z 367 [M+H]+.

Workup

  1. temperatureto reflux for 5 hrs
  2. temperatureThe reaction was cooled
  3. customthe organic layer was separated
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash chromatography with a gradient from 20-100% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d0c4d16b7b714b01a2446624cfa91ac6
Source dataset
uspto-grants-2011_05
Patent number
US07947728B1

Reaction notes

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